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DiMI Annual Report 2010 Periodic Management Report

Content

List of Participants _____________________________________________________________________________ 3

Periodic Management Report ___________________________________________________________________ 5

Section 1 – Justification of Major Cost Items and Resources __________________________________ 7

I. Work performed by each contractor during the reporting period 7

II. Explanatory note on any major cost item 24

III. A tabular overview of budgeted costs and actual costs (simplified) 30

IV. A tabular overview of budgeted person months and actual person months, by contractor and

by work package 34

V. Summary explanation of the impact of major deviations from cost budget and from person-

month budget 37

Section 2 - Form C Financial Statement per Activity for the Contractual Reporting Period ____ 39

Section 3 – Summary Financial Report (Summary Form C) ___________________________________ 40

Periodic Report on the Distribution of the Community's Contribution ________________________ 47

List of Participants 3


List of Participants

Participant Number

Participant Name Participant Institution Participant short name

Country Participa-tion (month)

1 = *CO Prof. Dr. A.H. Jacobs Universitätsklinikum Köln der Universität zu Köln

KUK D 1-60

2 Prof. Dr. J. Clark University of Cambridge UCAM-WBIC GB 1-60 3 Prof. Dr. S. Aime Università degli Studi di Torino UniTo I 1-60 4a 4b = 46

Prof. Dr. Guilloteau Prof. Dr. Benderbous

Tours University UniTours F 1-60

5 Prof. Dr. A. Planas Institut D’Investigacions Biomediques August Pi i Sunyer

IDIBAPS E 1-60

6 Prof. Dr. A. Maggi Università degli Studi di Milano Centro UNIMI I 1-60 7 Prof. Dr. G. Knudsen Copenhagen University Hospital RH-NRU DK 1-60 8 Prof. Dr. A. van der Linden Universiteit Antwerpen UA B 1-60 9a 9b = 28 9c = 30

Prof. Dr. C. Moonen Dr. L. Bridal Prof. Dr. P. Laugier Prof. Dr. R. Mastrippolito

CNRS France CNRS F 1-60

10 PD Dr. F. Bengel Prof. Dr. M. Schwaiger

Technische Universität München NUK_TUM D 1-60

11 Dr. H. Carlsen Prof. Dr. R. Blomhoff

University of Oslo UiO N 1-60

12a 12b = 23 12c = 38 12d

Prof. Dr. B. Tavitian Prof. Dr. P. Hantraye Dr. P. Rizo Dr. E. Ceccarelli

Commissariat a l’energie atomique CEA F 1-60

13 Dr. B. Brisson Biospace Labs BIOSPACE LABS

F 1-60

14a 14b = 41

Prof. Dr. V. Baekelandt Prof. Dr. K. van Laere Prof. Dr. A. Verbruggen

Katholieke Universiteit Leuven K.U.Leuven R&D

B 1-60

15a 15b = 16

Prof. Dr. D. Kirik Prof. Dr. A. Björklund Prof. Dr. T. Blom Prof. Dr. R. Holmdahl

Lund University ULUND S 1-60

17a 17b

Prof. Dr. D.J. Brooks Dr. H. Jones

Imperial College London Imperial College Lo

UK 1-60

18 Prof. Dr. I. Carrio Institut de Recerca del Hospital de la Santa Creu i Sant Pau

IRSCSP E 1-60

20 Prof. Dr. K. Ebmeier The University of Edinburgh UEDIN GB 1-60 21 Prof. Dr. B. Fleischmann Universitätsklinikum Bonn UKB D 1-60 22a 22b = 33

Prof. Dr. C. Halldin Prof. Dr. A. Nordberg Prof. Dr. Langström

Karolinska Institutet KI KI Neurotec

S 1-60

24 Prof. Dr. A. Bauer Forschungszentrum Jülich GmbH FZJ D 1-60 25 Prof. Dr. M. Hoehn Max-Planck-Institut für Neurologische

Forschung MPIfnF D 1-60

26 Prof. Dr. L. Hofstra Cardiovascular Research Institute Maastricht

CARIM NL 1-60

27 Prof. Dr. M. Horn Center for Bio-Imaging, Gothenburg University

CBI S 1-60

29a 29b

Prof. Dr. K. Leenders Dr. P.H. Elsinga

University Medical Center Groningen AZG NL 1-60

31 Prof. Dr. C.M. Morris University of Newcastle upon Tyne UNEW GB 1-60 32 Prof. Dr. K. Nicolay Technische Universiteit Eindhoven TU/e NL 1-60 33 = 34a Prof. Dr. S. Pappata Consiglio Nazionale delle Ricerche,

Instituto di Biostrutture e Bioimmagini CNR-IBB I 1-60

Periodic Management Report DiMI Annual Report 2010

Participant Number

Participant Name Participant Institution Participant short name

Country Participa-tion (month)

34 = 34b Dr. A. Auricchio Fondazione Telethon FTELE.IGM I 1-60 35 Prof. Dr. D. Parker University of Durham DUR GB 1-60 36 Prof. Dr. D. Perani Università Vita-Salute San Raffaele UVita-P I 1-60 37a = 37 37b

Prof. Dr. R. Poelmann Prof. Dr. C. Löwik

Leiden University Medical Center LUMC NL 1-60

39 Prof. Dr. E. Salmon Université de Liège ULG B 1-60 40a 40b

Prof. Dr. M. Schäfers Prof. Dr. C. Bremer

Universitätklinikum Münster UKM D 1-60

42 Prof. Dr. D. Vivien Cyceron CYCERON F 1-60 43 Dr. H. Carlsen Cgene, Oslo CGENE N 1-60 45 Prof. Dr. J. Masdeu Universidad de Navarra UNAV-FIMA E 1-60 47 J. B. Deloye Cyclopharma Cyclopharma F 1-60 48 Dr. S. Wecker medres – medical research GmbH,

Köln MEDRES D 1-60

50 Prof. I. Lukes Universita Karlova – Charles University, Faculty of Science

Charles University

CZ 1-60

51 Prof. Dr. R. Mikolajczak Radioisotope Centre Polatom POLATOM PL 1-60 52 Prof. E. Sykova Institute of Experimental Medicine,

Academy of Sciences of the Czech Republic

IEM ASCR CZ 1-60

53 Prof. Dr. L. Aigner Klinikum der Universität Regensburg KUR D 18-60 54 = 1 Prof. Dr. K. Herholz The University of Manchester UNIMAN GB 18-60 55 Prof. Dr. A.A. Lammertsma VU Medisch Centrum VUmc NL 18-60 56 Prof. Dr. B. Levkau Universitätsklinikum Essen UE D 18-60 **AP01 Prof. M. Kassiou University of Sydney AP Syd AU 18-60 **AP02 Dr. G. Pani UCSC Medical School, Rome AP Rome I 31-60 **AP03 Dr. P. Saladori CNR Institute of Clinical Physiology;

Pisa AP Pisa I 39-60

**AP04 Dr. L. Aigner Institut für Molekulare Regenerative Medizin Paracelsus Medizinische Privatuniversität, Salzburg

AP Salz AT 49-60

PERIODIC MANAGEMENT REPORT

DIMI

DIAGNOSTIC MOLECULAR IMAGING

A NETWORK OF EXCELLENCE FOR IDENTIFICATION

OF NEW IMAGING MARKERS

FOR DIAGNOSTIC PURPOSE

PROJECT NO.: LSHB-CT-2005-512146

START DATE OF PROJECT: APRIL 1ST 2005

DURATION: 66 MONTHS

PROJECT COORDINATOR NAME: PROF. DR. ANDREAS JACOBS

PROJECT COORDINATOR ORGANISATION NAME: KUK

PERIOD COVERED IN THIS REPORT: APRIL 1ST 2009 TO SEPTEMBER 30TH 2010

DATE OF PREPARATION: NOVEMBER 15TH 2010

SIXTH FRAMEWORK PROGRAMME

Section 1 – Justification of Major Cost Items and Resources 7


Section 1 – Justification of Major Cost Items and Resources

I. Work performed by each contractor during the reporting period

WP1 Ultra high resolution cerebral and heart imaging and quantitation with Single-Photon emitters

P13: Partner 13has validated the synchronization between the ECG module and the SPECT system with phantoms and healthy rats. P13 has developed a module for the 3D reconstruction of the optical signal after whole body optical acquisitions with the Photon Imager system combined with its additional module: 4View. Partner P13 has performed validation tests of the 3D reconstruction of the signal and evaluated the performance of the 3D BLI reconstruction in terms of quantification, sensitivity, spatial resolution, kinetics capabilities with P12b.

P12b: Partner 12 has given to partner P13 access to their animal facilities and provided BLI mouse models for partner P13 validation tests of its 3D reconstruction module.

WP2 Quantitative microPET and multi-modality (PET/MR, OT/MR) scanner development

P2 Installation and commissioning of the PET/MR scanner in the pre-clinical facility continues with the latest date for start of imaging activity planned for the last quarter 2010. This delay has been primarily due to a major failure of the CTI microPET consol requiring the establishment of a new support and service contract with Siemens. The consol is now repaired and calibration is underway and essential components, in particular a volume resonator and receive only surface coil compatible with the Bruker MR spectrometer are undergoing final test. The facility has passed initial inspection by the home office department charged with inspecting animal experiment facilities, and final inspection is planned for September 2010. Various personal and site licences has been granted by the home office. Use of the GATE Monte Carlo PET simulation package has progressed and is being used to evaluate the impact of RF coils on PET imaging. Also the reconstruction code STIR, Software for Tomographic Reconstruction http://stir.sourceforge.net/, has been adopted for image reconstruction of simulated data.

P5 Performance evaluation of PET scanners was standardized by the NEMA standards either for clinical PET scanners (2. ref- NEMA 2001) or for small animal PET systems (3-NEMA 2008 standards). The objective was to provide a baseline of the system performance independently of each camera’s design and specifications. Simulation studies were performed against the experimental measurements for the performance evaluation of the microPET R4 system according to the NEMA NU 4 2008 standards with three different MC codes. In addition, results were obtained from the simulation codes regarding the spatial resolution of the system. Experimental results were obtained for the microPET R4 system and using GATE. We also used the Monte Carlo application for simulation of geometrical PET scanners PeneloPET and results were compared to experimental data.

WP3 Development of radiopharmaceutical probes for neurodegeneration diseases

P4a: DAT tracer labelled with 18F or 11C, clinical evaluation, quantification, VAChT F18 tracers development, Amyloid plaques tracer development and characterization, tracers for the peripheral benzodiazepine receptors (PBR), clinical trials in the Amyotrophic Lateral Sclerosis (ALS) programme in Amyloid plaques (1[18F] FDDNP; [18F] AV-45) with authorization from the French agency,

8 Section 1 – Justification of Major Cost Items and Resources

AFSSAPs for a new clinical trial using [18F] AV-45. Serotonin transporter ligands synthesis and metabolism study, Synthesis of Alpha 7 ligands.

P7: Additional brain region templates from Hammers, UCL, London and Lyon, have been implemented in the software. Alpha 7 tracer labelled with 11C, clinical evaluation, quantification.

P12a: DAT tracer labelled with 18F or 11C, PBR tracer labelled with 11C. Alpha 7 ligands development.

P14b:

DAT tracer labelled with 18F or 11C, clinical evaluation, quantification, Amyloid plaques tracer development and characterization.

P22a: DAT tracer labelled with 18F or 11C, clinical evaluation, quantification, Amyloid plaques tracer development and characterization. Tracer metabolism. SERT tracers labelling with 11C.

P29b: Tracers for the peripheral benzodiazepine receptors (PBR) radiosyntheses and evaluation. Tracer metabolism.

P42: Synthesis of [18F] AV-45. Tracer metabolism. SERT tracers labelling with 11C.

P51: Preparation of tracers for DAT exploration (FE-CNT).

P55: Amyloid plaques tracer radiosyntheses (11C PIB and 18F FFDDNP). 11C Verapamil radiolabellings. Tracer metabolism.

AP Sydney: VAChT clinical and F18 tracers development, tracers and precursor for the peripheral benzodiazepine receptors (PBR), ALS programme.

Details by topic: DAT tracer labelled with 18F or 11C, clinical evaluation, quantification LBT 999, has been developed as a new DAT tracer for PET. This has involved the development of radiosynthetic procedures for 3H, 18F and 11C labelling and methods for purification and quality control. This tracer has been fully characterized in vitro and in vivo in animals. Toxicological studies have been completed in order to undertake a multicentre clinical research project. Complementary radiosyntheses have been made to be added to the French agency dossier (IMPD). KI developed a promising fluorinated DAT agent, the FE-PE2I. This new radioligand has been fully characterized, in vitro and in vivo in non human primate. DAT radiotracers labelled with 18F or 11C (radiosyntheses and optimisation of the radiolabelling, metabolism studies) were performed in Orsay.

VAChT clinical and F18 tracers development New synthesis of reference and precursor of FPOBV has been engaged. Radiosyntheses of FPOBV were realized for biological characterization of the tracer.

Amyloid plaques tracer development and some in vitro test For amyloid plaque imaging, the labelling of 11C PIB is performed in Leuven. New fluorine-18 labelled analogues based on the 2-phenylbenzothiazoles structure have been developed and have been evaluated in vitro in Leuven. In addition [18F] AV-45 radiolabelling has been successfully performed in Tours and Caen, and the documentation for approval to use in human has been prepared (investigational medicinal product dossier: IMPD) and accepted by the French Authorities (AFSSAPs). Multicentre clinical trial using [18F] AV-45 already started. Clinical investigations using [18F] FDDNP are still in progress in Tours. Amsterdam use 11C PIB and 18 FDDNP with a GMP certificate in clinical research trials. On the basis of in vitro affinity studies on post mortem brain homogenates of patients with Alzheimer’s disease (AD) (A. Verbruggen in cooperation with Prof. H. Kung, Philadelphia) and in vivo



biodistribution studies in mice and rats, an 18F labelled 4-fluorophenylbenzothiazole has been selected for clinical evaluation in AD patients. Toxicity data have been generated in accordance with the microdosing concept (14-day follow-up study in rats using the equivalent of 1000x intended human dose + two genotoxicity tests). The product appears to be safe and an investigational medicinal product dossier (IMPD) has been composed and submitted to the authorities for approval of a clinical evaluation study. Approval for the start of a clinical evaluation in 10 AD patients and 10 healthy volunteers has been obtained. KI evaluated AZD2184 as an amyloid plaques imaging agent. In vitro and in vivo imaging in baboon was performed. Tracers for the peripheral benzodiazepine receptors (PBR) DPA-713 and DPA-714 have been synthesised and evaluated as potential PET tracers for the PBR. Radiosyntheses of 11C DPA-713 has been performed to fully characterize the ligand (animal models, microPET studies). DPA-714 has been labelled using fluorine-18 using an automated synthesis module in clinical trials. Radioligands were injected to control and patients with Amyotrophic Lateral Sclerosis (16 patients). Tracer metabolism studies started in control and patients. Amsterdam and Groningen also started to work with these radioligands. 123I CLINDE has been prepared and evaluated in animal models. Radiosyntheses of 18F DPA-714 (on a TRACERLab FX-FN, SHFJ-Orsay) have been performed to fully characterize the ligand (animal models, rodent and non-human primates, microPET studies). In vitro metabolism studies of 18F DPA-714 have also been performed (SHFJ-Orsay).

Tracer metabolism Metabolism of 18F-FECNT, a high affinity (Kd= 6 nM) dopamine transporter tracer with a tropane structure, bearing a [18F]fluoroethyl group on the carboxyl and a chloro substituent on the 2-phenyl group, has been studied in plasma, cerebrum and cerebellum of rats at 30 and 60 min after intravenous injection. The tracer agent appears to be significantly more stable (about 90 % intact tracer after 60 min) than other reported tropane derivatives used as DAT tracer and could constitute a stable and interesting PET-tracer replacement for existing DAT-tracers with interfering metabolites. Partner 22a investigated [11C] PE2I metabolism in human and [18F]FE-PE2I in rodent and monkey. Concerning [11C] PE2I, the plasma analyses demonstrated that more polar radiolabelled compounds than the parent compound are present. The BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. It suggests that the difference may be explained by the inaccurate metabolite correction and that theses metabolites affect the DAT quantification. Metabolism of 11C MADAM, a serotonin transporter ligand, has been studied in rat and monkey. 11C MADAM is a highly potent SERT ligand that possesses a sulphur atom. As sulphur can potentially be oxidized, a LC/MS/MS study was perform in both species to determine if oxidized forms of 11C MADAM can be generated and in that case may affect the SERT quantification. [11C]SOMADAM was not detected in rat brain and is only a minor labeled metabolite of [11C]MADAM measured in monkey plasma. In addition, [11C]SOMADAM is not superior over [11C]MADAM as a SERT PET radioligand. Metabolism studies of [11C]AZD2184 were performed.

Implementation of in-house made software packages in DiMI-laboratories Additional brain region templates from Hammers, UCL, London and Lyon, have been implemented in the software. The data have been submitted as an abstract for SNM 2010.

New labelled tracer for alpha7-nicotinic receptor molecular imaging The high-affinity alpha7-nAChR selective orthosteric agonist NS14492 was radiolabelled by methylation of its precursor using [11C]methyl triflate and brain kinetics investigated with PET in five female Danish Landrace pigs at baseline and after i.v. administration of blocking compounds. New fluorinated alpha 7 ligands were developed in Tours, two were fluorinated with 18F. Alpha 7 radiotracer (development of a radiotracer labelled with 11C) performed in Orsay.

Ex vivo and in vivo testing of monoaminergic antagonist and agonist tracers Nine different novel serotonin 2A agonist radioligands have been tested ex vivo in the pig with PET in Copenhagen.


WP4.1 Development of library of innovative MRI probes and improved methods for “in vivo” cellular labelling

The major cost items related to the work done within WP 4.1 dealt, as in the last year, with i) the salary of PhD students and post-docs, and ii) the cost of consumables and instrumentations associated with the work performed. Minor cost items were travel costs for conference attendance, joint meetings and short course training.

Briefly, the work performed by each unit dealt with:

P3: Synthesis of a novel ligands for Ln(III) ions designed to prepare i) improved Gd(III) complexes able to report about MMP activity, and ii) amphiphilic PARACEST agents designed to increase the sensitivity in the detection of MR-CEST contrast; development of a fibrin-targeted LipoCEST agents and polymersome-based T1 and CEST agents; set-up of a MRI multicontrast kinetic protocol to assess the intratumor trafficking of liposomes; preparation of a dual pH responsive 19F/1H MRI agent.

P14a & P25: Cell labelling experiments on stem cells; set-up of in vitro protocols for assessing the expression of i) MMPs by dendritic cells, and ii) glutamic acid decarboxylase by GABAergic neurons; preparation and characterization of monodisperse magnetic core particles.

P32: Development of a 19F MR-based method for quantifying integrin targeted paramagnetic perfluorocarbon emulsions; studies on binding property of CNA35 peptide, loaded in lipid-based nanosystems like micelles and liposomes, to collagen; kinetic investigation of the intracellular trafficking of contrast material.

P35: Cell labelling experiments for assessing the intracellular trafficking of emissive lanthanide complexes: preparation of paramagnetic lanthanide complexes labelled with 19F spins to develop pH sensors.

P50: Synthesis of Gd(III) complexes to be loaded to nanosystems.

WP4.2 Development of optical and combined imaging probes

P35: Developed the creation of conjugates for study in magnetic resonance imaging and spectroscopy studies as well as the definition of optical imaging probes for intracellular use (objectives 2 to 5)

P3: Examined the behaviour of nanoparticles for dual imaging studies in cooperation with P50 and in part with P35.

P50: Continued to develop with P3 the synthesis and characterisation of conjugates of lanthanide complexes for use in MR experiments cited in WP 4.2.

WP5 Animal library for diagnostic molecular imaging in neuroscience and cardiovascular

P5: PET studies were carried out in a stroke animal model (Martin et al., 2009). Collaboration with P8 in a MRI study in a model of Huntington’s disease (Van Camp et al., Neurobiology of Aging, in press). Collaboration with P14b in an animal model of Huntington’s disease (Casteels et al., Eur J Nucl Med & Mol Imag in press). We developed a model of chronic brain hypoperfusion and MRI studies were carried out (Soria et al., manuscript in preparation). We showed the benefit of antioxidant treatment in a stroke model (Perez-Asensio et al., 2010) and we carried out an MRI study (Soria et al., in preparation). We developed a transgenic mouse model expressing fluorescent mPlum under the promoter of Hsp70 and subjected it to brain ischemia (manuscript in preparation). We transferred these animals to P9a and we carried a collaborative study.

P1:



This partner carried multimodality imaging in mouse models of neurological diseases and produced a publication on this subject (Waerzeggers et al., 2010).

P6: This partner was interested in inflammation in Alzheimer’s disease and studied the formation of atherosclerotic lesions in transgenic mice overexpressing the beta-amyloid precursor protein (Tibolla et al., 2010). They also used reporter mice and produced a publication on this subject (Maggi and Rando, 2009).

P7: Studies carried out by this partner identified alterations in the expression of the serotonins 2A receptor as surrogate markers of amyloid deposition in a mouse model of Alzheimer’s disease (Holm et al., 2010). They also studied alterations in this receptor in relation to BDNF expression in cell cultures (Trajkovska et al., 2009) and used conditional brain-derived neurotrophic factor knock-out mice (Klein et al., 2010).

P8: By carring MRI studies in animal models of Parkinson’s and Huntington’s diseases, a number of collaborations were done by this partner with P5, P14a, P14b that resulted in several publications (Van Camp et al., 2009; 2010; 2010 Neurobiol Aging (in press)).

P9a: This partner is interested in reporter mice to image heat shock responses, and has used mPlum transgenic mice under the promoter of Hsp70 provided by P5. A manuscript is in preparation.

P10: This partner identified targets and used new imaging strategies for imaging of vascular inflammation in atherosclerotic mice (Laitinen et al., 2009) and in models of myocardial infarction (Sherif et al., 2009).

P11: This partner collaborated in the generation of the mPlum mice by P5.

P12a (additionally): This partner did not initially participate in this WP, but in this last period they made an important contribution, as they image brain inflammation with PET using 18F-DPA-714 in an animal model of stroke and showed the possibility to discriminate by PET the effects of an anti-inflammatory treatment with minocycline (Martin et al., 2010).

P14a: Collaborations with P8 and P14b in imaging an animal model of Parkinson’s diseases produced several publications (Van Camp et al., 2009; Casteels et al., 2010). Also this partner who has worked intensively in gene transfer using viral vector technology has studied transgene expression in the brain using small epitope tags (Lobbestael et al., 2010). Finally, this partner conducted a task Identification of metabolic markers, indicative for etiology of brain abscesses and non-invasive monitoring of treatment success of brain infections. Several publications derived from these studies (Himmelreich et al., 2009; Krockenberger et al., 2010).

P14b: This partner has also been actively collaborating within the network by carrying PET studies in animal models of Parkinson’s and Huntington diseases, and this work produced several publications (Casteels et al., 2010, Casteels et al. Eur J Nucl Med & Mol Imag in press; Van Camp et al., 2009, 2010).

P15a: This partner developed viral vector-mediated gene transfer technology using adeno-associated viruses.A study was published (Kornum et al., 2010).

P21: This partner, in collaboration with P32, treated mice with embryonic cardiomyocytes, skeletal myoblasts, or mesenchymal stem cells, in the infarct centre, immediately after induction of myocardial infarction, and functional recovery was assessed using MRI at 2 weeks after the treatment. Results of this study will be part of a publication in preparation.


P25: This partner did sophisticated MRI studies in animals to image brain activation with high filed MRI (Seehafer et al., 2010) and carried several MRI and optical imaging studies in vitro and in vivo with view of application to stroke models (Kruttwig et al., 2010, Nohroudi et al., 2010).

P32: This partner developed and evaluated several contrast-enhanced MRI methods for the assessment of myocardial ischemia in mice. A new method to measure the blood perfusion of the mouse myocardium was developed. The possibility to use MRI for quantification of wall shear stress (WSS) in apoE-/- mouse model of plaque was investigated. In collaboration with P21, this partner also evaluated with MRI the improvements in heart function induced by stem cell treatment in mice with myocardial infarction. The results of these studies produced a number of publications (Coolen et al., 2010, 2010; Mulder et al., 2009, 2010; Strijkers et al., 2010; van Bochove et al., 2010).

P34: This partner did several studies on gene transfer with adeno-associated virus (Bello et al., 2010; Tessitore et all., 2010; Colella et al., 2009, Cotugno et al., 2010), and developed imaging strategies using PET for imaging gene transfer (manuscript by Cotugno et al. under revision in Human Gene Therapy).

P40a: A preclinical evaluation of an 18F-labelled beta1-adrenoceptor selective radioligand by PET to image cardiac alterations was carried out by this partner (Law et al., 2010).

P42: This partner developed new models of stroke and imaged new targets by using tPA labelled with paramagnetic particles for MRI. Two papers are under review at the present time using these models (Macrez et al.) and a third one is in preparation

P54: PET studies were carried out to image brain inflammation in corpulent rats using the PBR ligand 18F-DPA-714, A manuscript by Boutin et al. is in preparation.

P56: PET and MRI studies were carried out to characterise progressive heart failure in cardiac-specific S1P1 knockout mice. This work will contribute to a future publication.

WP6 Evaluation of the role of estrogen receptors in a mouse model of Alzheimer’s disease and generation of novel reporter systems

P6: We generated within DIMI a novel reporter mouse for the study of neuroinflammation (the PPRE-Luc) which in the past year has been applied to the investigation of the involvement of PPARs in a specific pathology (ALS) leading to neurodegeneration. Moreover, we studied PPAR activity in the PPRE-Luc, hSOD1G93A in relation to the progression of the disease. We studied ER activity in these models also in relation to the disease.

WP7 Non-invasive phenotyping of animal models for neurodegenerative diseases

P8: Developed and optimized a MR imaging protocols were applied in a longitudinal study of transgenic HD rats and in transgenic rat pups. Cost items and resources: Personnel, gas anaesthesia (isoflurane, oxygen and nitrogen), MRI use, transport and housekeeping of animals, MRI system use, workstation for data processing, labour and travel expenses for WP7 meetings

P1/25: To accomplish the protocol for measuring brain activation by FDG microPET after electrical forepaw stimulation a non-invasive method for quantification of cerebral glucose metabolism in rats using an extra-cerebral reference region has been developed and validated. Cost items and resources: personnel, animals and animal housing, anaesthetics, use of PET and radioligands, histology, travel expenses



P3: work on hold, waiting for data input

P5: We worked on the use of repeated MRI studies with DWI during and shortly after a transient episode of brain ischemia as an early predictor of infarct volume in a rat model of stroke. -Cost items and resources: rats (including animals, housing), chemicals, immunohistochemistry, histology, use of animal MR-system.

P6: Working on the identification of novel methodologies to study ER expression in brain by optical imaging, reported in WP6. Cost items and resources: Mice breeding, mouse phenotyping (PCR/southern analysis), laboratory disposables.

P12a: Accomplishment of a longitudinal μPET study on transgenic rat models of Huntington’s Disease looking at brain metabolism and dopamine-2 receptor binding.

P14a: Switched to adeno-associated viral vectors for the development of viral vectors for imaging of neurodegeneration. Optical imaging of protein-protein interactions in vivo. Bioluminescence imaging costs. Cost items and resources: Consumables for molecular biology (lentiviral constructs), cell cultures, histology, animal costs, equipment for surgery, microtome, stereological quantification

P14b: Micro-PET imaging of dopaminergic neurodegeration in the LV-SYN-based rat model: longitudinal study [18F]-FECT micro-PET. We evaluated the capability of THC, a plant derived cannabinoid, to alter the progress of neurodegeneration in the quinolinic acid (QA) rat model of Huntington’s disease. Cost and resources: Housing of all animals, tracer production for CB1/ FDG imaging in LV alpha-syn rat model/ QA rat model/ and TgHD rat model, purchase of THC for therapy evaluation in QA model

WP8.2 Early diagnosis of neurodegenerative disease

P54: Coordination of the project, data analysis for PIB PET meta-analysis and preparation of manuscripts, publications, talks and presentations, reporting

P1: Help in coordinating the project, reporting, joint analysis of clinical and neuropsychological data for the PIB PET meta-analysisd

P7: Inclusion of AD and MCI patient cohorts with follow-ups; implementation of a new volume of interest analysis, available for analysis of molecular images across centres via download; presentation and publication of results.

P10: Neuropsychological follow-up studies have been performed; PET, clinical and neuropsychological data was provided to the data base mask prepared by P1/P54; presentation and publication of results.

P14b: Contribution of an MCI patient cohort; initiation of a follow-up study of healthy controls; investigation of new radioligands (e.g. 18F-flutemetamol) and its relation to 11C-PIB in phase I and phase II studies; investigation of other targets based on genetic screening and recent literature in AD, e.g. cannabinoid type 1 and type 2 receptors and other endocannabinoid related targets; presentation and publication of results.

P17a: Participation in discussion and communications on joint PIB PET meta-analysis

P20: Presentation and publication of results.


P22a: No activities reported within this WP.

P22b: Submission of MCI, AD and control data to PIB PET meta-analysis; analysis of the relation of PIB retetntion and CSF biomarkers in MCI patients; data analysis in PIB PET meta-analysis (Agneta Norderberg from P22b is the first author of the manuscript that is being prepared; study on the influence of ApoE genotype on PIB retention in MCI and AD patients; initiation of longitundinal PIB PET studies in subject at risk for familial form of AD (mutation carriers); presentation and publication of results.

P31: Work for Deliverable 8.2.16 “Validation of neuroimaging targets in the DLPFC and Caudate”: Completion of microarray analysis of the dorsolateral prefrontal cortex and anterior aspects of the caudate nucleus in healthy subjects and depressed subjects; listing of differentially expressed genes to P1 for consideration as patenting targets; presentation and publication of results.

P33: Completion of the clinical and neuropsychological 1 year follow-up in MCI patients; discussion of the data analysis performed on SPECT-123I-iomazenil images obtained in controls, MCI and AD patients at the annual DIMI meeting 2009 in Barcelona; planning of a combined data analysis of data obtained with PET-11C-flumazenil and SPECT-123I-iomazenil in AD patients together with P45; presentation and publication of results.

P36: Completion of PET acquisition, documentation and submission of clinical follow-up data in MCI and dementia patients and participation in MP3 meta-anylsis; development of a new method for quantitative measurements of acetylcholinesterase (AChE) activity by 11C-MP4 and PET, based on a Bayesian approach; analysis and provision of evidence for functional reserve in both ApoE4 carriers and non-carriers AD patients in a multicentric FDG PET study within DIMI project; completion of a 2 year scientific exchange with the research group of Prof. Andreas Bauer, Forschungszentrum Juelich (Dr. V. Garibotto stage); presentation and publication of results.

P39: Perfomance of follow-up study of MCI patients; exchanges with partner P14b and group leader (P1) for further studies on amyloid imaging; Preparation of PET/CT/MRI setting for small animals at the Cyclotron Research Centre at the University of Liège; formation for modelling and software for image processing (meetings Bergen; Lyon; Copenhagen; Zurich); presentation and publication of results.

P45: Completion of study and analysis of FDG and Flumazenil PET in patients with microvascular brain disease, with and without dementia, and AD; presentation and publication of results.

WP9 Neuroinflammation

P7: Protocol written for approval of ethical committee regarding use of 123I-CLINDE in patients with neuroinflammatory disorders. Paper written and published regarding cerebral region of interest delineation. The remaining work is described under WP3, WP5, WP8.2, and WP15.

P4a: DAT tracer labelled with 18F or 11C, clinical evaluation, quantification, VAChT F18 tracers development, Amyloid plaques tracer development and characterization, Tracers for the peripheral benzodiazepine receptors (PBR), clinical trials in the Amyotrophic Lateral Sclerosis (ALS) programme in Amyloid plaques (1[18F] FDDNP; [18F] AV-45) with authorization from the French agency, AFSSAPs for a new clinical trial using [18F] AV-45. Serotonin transporter ligands synthesis and metabolism study. Synthesis of Alpha 7 ligands.

P5: A former post-doctoral student of our team carried experiments intended to demonstrate that it is possible to monitor the anti-inflammatory effect of a treatment by PET using a ligand of PBR. Due to advantages in the economic costs and the availability of better PBR ligands than [11C]PK11195, we



decided to carry this study in Orsay using [18F]DPA-714. The study was carried out by partner P12a. The drug used was minocycline, which reduces microglial activation and has anti-inflammatory properties. The results showed that minocycline administered daily during 7 days after ischemia decreases [18F]DPA-714 binding, in agreement with anti-inflammatory activity of this drug. Therefore, this study shows that [18F]DPA-714 PET is a useful biomarker to image the effect of anti-inflammatory strategies in experimental cerebral ischemia. The study has been recently published (Martin et al., 2010; Mol Imaging Biol. 2010 Apr 10. [Epub ahead of print]).

P22a: (1) Post mortem autoradiographic studies on human whole hemisphere brain slices, obtained from Alzheimer patients and age matched controls, with the “golden standard” PK11195 and novel DAA11ö6 analogues. Two papers written and published. (2) Two manuscripts, describing earlier in vivo studies with radiolabelled PK11195 and vinpocetine in ageing control subjects, Alzheimer patients and stroke patients, were finalized and prepared for submission in August 2010.

P22b: Protocol written for approval of ethical committee for studies of 11C-deprenyl , 11C-PIB, 18F-FDG in MCI patients, AD patients and subject at risk (familial AD). Data for MCI and AD patients presented at ICAD 10. Ms under preparation

P33: Data analysis of FDG and MRI images in MS patients and of DWI images in controls. Further development and validation of digital phantom. Upgrade of the paper on digital phantom with the description of the new features and resubmission. Paper has been written and published on VBM analysis of MRI brain volume in MS patients. Paper has been written and published using DWI data in controls. Implementation of 18FDPA-714 synthesis and first PET studies of biodistribution in mice. Synthesis of DPA-714 precursor.

P36: Rodent studies with [F-18]VC701: manuscript is ready to be submitted. Patients studies: data analysis of PET [C-11]PK11195 images. Papers under preparations.

P42: Last in vivo experiments were performed to validate the use of Alexa-555- / Alexa-680- / MPIO-labelled tPA for multimodal imaging of the passage of tPA across the blood brain barrier in a model of thromboembolic stroke in mice. Paper in preparation.

P54: Clinical: Implementation of the supervised, clustering approach for the PK-11195 PET analysis (in collaboration with Hammersmith). Scanning and analysis of a cohort of normal volunteers on the HRRT camera. Preclinical: Scan of a co-morbidities model for stroke (JCR-LA, corpulent) rats with [18F]DPA-714 at 9, 12 and 15 months of age; manuscript going to be submitted to JCBFM. Completion of the biodistribution study of [18F]IL-1RA, writing of the manuscript, submitted to Br. J. Pharmacol.

P55: A modified version of the supervised cluster analysis algorithm for extracting a reference tissue input function from dynamic PK11195 PET brain studies has been implemented. The main advantage of this modified version is a reduction in number of clusters (4 instead of 6), making it less sensitive to noise and less scanner dependent. The performance of the new method has been evaluated extensively against both the original 6 cluster method and using cerebellum as reference region. Superior performance with respect to the ability to detect differences in specific binding between young and elderly controls and MCI and AD patients was observed using the modified 4 cluster method compared with the other 2 methods. An oral presentation was given during the BrainPET09 meeting in Chicago and a manuscript is presently in preparation.

WP10 Stem cell trafficking in the CNS

P1: Partner 1 evaluated together with P25 the eNSC niche by �18F�-FLT PET and the effect of neural stem cell therapy on functional recovery after stroke by fMRI, electrophysiology and behavioural tests.


P3: Partner 3 synthesized and evaluated Gd-chelates that are responsive to the activation by matrix metalloproteinases or GAD (together with P25 and P14a(H)).

P8: Partner 8 performed MRI studies to investigate the modified migration of endogenous neural progenitor cells after in situ labelling with iron oxide contrast agents in a mouse model of central nervous system demyelination and in a mouse model of Huntington’s disease. Furthermore, the multimodal labelling strategy for neural stem cells (NSC) as well as for bone marrow-derived stromal cells (BMSC), based on (i) genetic modification with both the eGFP and Luciferase reporter genes, and (ii) endocytic uptake of blue fluorescent magnetite-containing micronsized particles was optimised and tested in vivo

P12b: Partner 12b performed �18F�-Fallypride imaging of striatal grafted Parkinsonian rats with the aim to monitor synaptic changes in dopamine levels in vivo these grafted animals.

P14a: Partner 14a investigated the effect on endogenous neurogenesis after pharmacological activation (dopamine D3 receptor antagonists) or in disease models of stroke (photothrmombotic model and MCAO model) and parkinson’s disease (overexpression or downregulation of the Parkinson-related gene DJ-1). P14a(H) synthesized and evaluated highly monodisperse SPIOs for cell labelling and evaluated Gd-chelates that are responsive to the activation by matrix metalloproteinases or GAD (together with P25 and P3). Furthermore the specificity of MR contrast generated by engrafted cells (MSC, NSC or fibroblasts) labelled with SPIOs in a photothrombotic stroke model was investigated and the MR labelling protocol for visualisation of cell migration over short distances optimised and tested in vivo.

P15a: Partner 15a conducted behavioural and biochemical testing of striatal grafted Parkinsonian rats with the aim to unravel the mechanisms of graft-induced dyskinesia.

P25: Partner 25 evaluated Gd-chelates that are responsive to the activation by matrix metalloproteinases or GAD (together with P3 and P14a(H)). Together with P53 a multimodality imaging protocol (BLI and MRI) was worked out to follow endogenous neurogenesis and ischemic lesion evolution in a stroke model (MCAO model) and together with P1 the effect of neural stem cell therapy on functional recovery after stroke was investigated by fMRI, electrophysiology and behavioural tests.

P32: Partner 32 evaluated and optimised the cell labelling properties of a targeted MR contrast agent (a paramagnetic RGD-conjugated agent targeting �v�3 integrin expressing cells) and a self-developed dual SPECT/MR contrast agent. Furthermore, P32 investigated the effect of stem cell therapy on functional recovery after myocardial infarction by MRI (in cooperation with P21, linked to WP11.2 and 12).

P37b: Partner 37b investigated on a cell culture level the feasibility to use EPI-NCSCs derived from DCX-RFP transgenic mice to non-invasively image neuronal differentiation and of EPI-NCSCs derived from GFAP-luc transgenic mice to non-invasively image glial differentiation. Moreover, a new LV reporter construct was developed containing membrane-bound humanized Gaussia luciferase with the aim to create a new sensitive reporter for stem cell trafficking.

P52: Partner 52 manganese perovskite nanoparticles and a novel bimodal contrast agent containing fixed Gd complexes conjugated with fluorescein were synthesized, characterized and used to label rat and human mesenchymal stem cells. MR spectroscopy (MRS) was used to monitor metabolite changes in an experimental model of stroke in rats and in the contralateral hemisphere after the intrastriatal administration of neural stem cells derived from human induced pluripotent cells (iPS-NPs) in order to study the impact of the cell treatment on the brain tissue four months after transplantation.

P53:



Partner 53 together with P25 a multimodality imaging protocol (BLI and MRI) was worked out to follow endogenous neurogenesis and ischemic lesion evolution in a stroke model. Furthermore P53 generated and validated a new transgenic mouse line (DCX-promoter-CreERT) that allows for tamoxifen-inducible imaging reporter expression in neuronal precursors and assessed the activation state of the TGF-beta signalling cascade in the hippocampal neurogenic niche under physiological and neurodegenerative (HD) conditions.

WP11.1 Multimodality characterization of atherosclerotic plaques

P40a: Work was focussed on the evaluation of new tracers such as MMP inhibitors and caspase inhibitors in experimental animal models of atherosclerosis. A new mouse model suffering from spontaneous myocardial infarctions was established and initially characterized.

P2: Work has focussed on the production and validation of the TSPO/PBR radioligand 18F-FEDAA1106 and the development of partial volume correction applied to FDG-PET in several human studies.

P10: Evaluation of 18F-Galacto-RDG for imaging inflammation in atherosclerosis in a double knock-out mouse model (in vivo microPET/CT, validation in tissue samples using autoradiography and immunohistochemistry).

P18: Imaging experiments on APOE- mice after arterial ligation.

P26: In a study in patients with significant carotid artery lesions we observed that Annexin A5 not only bound to apoptotic cells, but also to activated and stresses cells, such as activated macrophages and aging red blood cells.

P27: In a phantom with variable slice thickness of X-ray contrast agents MRI measurements were performed. In a second step, the phantom was modified in order to allow online mix of discrete amount of contrast agents. No adverse effects on image quality were found with standard clinical contrast agents for X-ray and MR. Atherosclerotic plaque in ApoE mice was induced by 4 month of high fat diet. Animals were examined by MR before and after an injection of a single dose (0.2 ml) of X-ray contrast agent in the tail vein. No effects on image quality were seen during examination.

P32: The phenotype of plaques, induced by the application of a tapered cast in the carotid arteries of ApoE-/- mice, was studied with respect to collagen content and MMP activity. Collagen content was visualized using a collagen-targeted bi-modal micellular contrast agent, equipped with a Gd label for MRI and a near-infrared label for fluorescence imaging. Stable plaque phenotype shows more enhancement upon application of the agent, in agreement with a higher collagen content. A Gd-based low-molecular weight MR contrast agent was for determination of MMP activity. MMP-activity will be further studied in the next period.

P37a: Atherosclerotic plaque development in ApoE-/- mice induced by carotid cuff or by diet has been studied with the use of micelles. Untargeted Gd-micelles are able to penetrate the vessel wall, more so in plaque areas. The peak contrast is determined over time using MRI. Targeted micelles will be used in the next period to determine the plaque constituents and whether plaque phenotypes can be discriminated in vivo.

P40b: Apo E-/- mice underwent fluorescence reflectance imaging as well as fluorescence mediated tomography to assess binding of a previously developed integrin-binding fluorochrome. Phantom experiments were performed to co-register MRI and FMT data with a new ‘free space’ FMT system. Moreover a non-peptidic MMP binding fluorochrome was successfully synthesized and characterized in vitro and in vivo.

P56:


Ex vivo Micro-CT of embedded aortic tissue of ApoE-/- mice has been performed after optimization of preparation techniques, embedding procedures and adaptation for co-registration. Further evaluation of the procedure and fusion of images will be performed in the next period

WP11.2 Characterization of myocardial angiogenesis

P10: Characterization of 18F-gRGD for imaging of myocardial angiogenesis and post-MI remodelling. Development of reporter gene PET imaging for monitoring survival of progenitor cells after cardiac transplantation.

P09a: Not active during this period.

P9b: Characterization of ultrasound techniques for imaging blood flow and angiogenesis in tumor models.

P14b: Not active during this period.

P21: Functional imaging of stem cell therapy for experimental myocardial cryo-injury.

P26: No reply

P32: Functional imaging of stem cell therapy for experimental myocardial cryo-injury. Development of MRI techniques and characterization of new contrast agents for imaging myocardial injury.

P37a: Characterization of new MRI contrast agents.

P40a: Characterization of new mouse model with spontaneous myocardial infarctions. Comparison of PET and MRI imaging of myocardial injury.

P40b: Not active during this period

WP12 Cardiac stem cell therapy monitored by molecular imaging

Part of the work reported by P9a was carried out in collaboration DiMI partner P37b. Part of the

work reported by P21 was carried out in collaboration DiMI partner P32. P1 actively contributes to

the discussions but decided not to contribute actively to the work of JPA4.

Detailed reports on JPA4 activities were obtained from all partners participating in the elaboration

of JPA4 and have been included in the Periodic Activity Report with specific contributions for each

partner. A summary of highlights is included below.

Discussions between WP10 and WP12 (both WPs deal with stem cells, but in different organs) have been strengthened to identify mutual interests as recommended by the reviewer. A selection of highlights of this period will be reported below for each of the objectives

1. employing external markers and reporter genes for evaluation of stem cell differentiation

Transplantation of FACS-sorted ES-cell-derived early mesodermal precursors was

performed to achieve complete restoration of cardiac tissue by cardiac, endothelial as well as

mesenchymal differentiation.

Using immunohistochemistry the differentiation of the injected human epicardial derived stem

cells (EPDCs) was established. No “new” cardiomyocytes were detected and no vascular

profiles were formed from the EPDCs, However, more vascular profiles from the host

vasculature were present, proving the paracrine influence of the injected cells.



2. optimization of imaging biomarkers for functional assessment of stem cell therapy in a

cardiac ischemia model

Paramagnetic iron was used to ease the tracking of injected stem cells in the infarct zone of a mouse heart in vivo. Afterwards the histological assessment confirmed the location of the injected cells. Echocardiographic characterization of the left ventricular morphology of the mouse heart has shown to be relevant in genetically engineered mice in order to study cellular and sub-cellular processes, disease development and progression and possible strategies for therapy. In addition, echocardiographic experiments provide real time information about cardiac cycle with high accuracy what MRI can’t provide. Embryonic cardiomyocytes, skeletal myoblasts and mesenchymal stem cells were incubated with USPIOS and liposomes. Different concentrations of the contrast agents as well as different incubation times were evaluated. To visualise cell engraftment prior to MRI scan luciferase labelling of transplanted cells was established.

3. assessment of the feasibility of imaging stem cell differentiation in a cardiac ischemia model

The issue of stem cell differentiation, and their functional integration, in the heart has been

studied in much detail in WP12, with excellent results. The results of those studies clearly

point to the difficulties of stem cell differentiation, and functional integration, in the heart in

vivo. Those very results have many implications for clinical translation of the use of stem

cells.

4. characterization of the efficiency of spatiotemporal control of differentiation

Mesenchymal stem cells differentiate into osteoblasts under the influence of the bmp7 or

Runx2 gene products. Conditional expression by heat of these two target genes for

differentiation should allow spatiotemporal control of differentiation. New modified cell lines

containing both a “differentiation gene” (BMP-7 or Runx2) and a reporter gene (Firefly

luciferase) under the control of a heat sensitive promoter (Hsp70) have been obtained,

permitting combination of differentiation induction and assessment of correct heating by

HIFU in vivo. First in vitro experiments of these modified cell lines gave positive results with

osteoblastic differentiation after heat shock (water bath).

Modulation of gene expression of the luciferase marker gene was shown to be possible by

changing temperature and/or duration of regional heating. Mild heating protocols were

sufficient for significant gene activation without causing tissue damage.

5. improvement of temperature mapping in view of spatiotemporal control of differentiation with

heat

Classic multi-baseline thermometry correction approaches use a complete collection of

reference magnitude and phase images constructed before thermal therapy. An alternative

correction method was proposed consisting of two steps: a linear magnetic field perturbation

model is computed in a preparative step; subsequently, during the intervention, this model is

used to reconstruct the magnetic field perturbation corresponding to the actual organ position

in real-time, which in turns allows computation of motion corrected thermal maps. The

proposed approach presents several advantages compared to the existing multi-baseline

approach: improvement of accuracy on temperature maps, an improved robustness with

respect to local and global intensity changes, and a non-negligible computational time

acceleration that makes the proposed work compatible with the real-time thermotherapy

constraint. This approach is suitable for Real-Time cardiac temperature mapping and

visualization.


6. exploration of the relationship between quantitative values derived from cell therapy and

functional changes

The global effects of skeletal myoblast (SM) and mesenchymal stem cell (MSC)

transplantation on infarcted mouse hearts were studied noninvasively with in vivo contrast

enhanced cardiac MRI. Both cell types were isolated from Swiss mice to enable a direct

comparison. Myocardial infarction was induced in male Swiss mice by either cryoinjury or

permanent occlusion (ligation) of the left coronary artery, immediately followed by injection of

PBS (sham) or GFP-positive SM or MSC in the centre of the infarction. Cells were isolated

from 17.5d embryos and adult mice respectively. Non-operated Swiss mice served as

controls. Two weeks after the induction of myocardial infarction, infarct size was reduced by

transplantation of either SM and MSC in both cryoinjured and permanently occluded hearts.

Ejection fractions (EF), end-diastolic and -systolic volumes (EDV and ESV, respectively)

were improved in all treatment groups, except for mice with cryoinjury transplanted with SM.

However, all functional parameters were still impaired compared to control mice. End-

diastolic mass was decreased by ~17% in mice with permanent occlusion transplanted with

SM or MSC, whereas only a minor decrease was found in mice with cryoinjury. Therapy was

most effective in mice with permanent occlusion, where relative infarct size was decreased

by 13.8% and 34.5% after transplantation of SM and MSC respectively. This was

accompanied by an increase in EF of 24.8% and 63.6%, achieved by a reduction in EDV and

ESV of 30-40%.

Work on PET of EPCs labelled with the reporter gene NIS after injection into rat myocardium after ischemia-reperfusion injury has been started. Initial studies indicate that the lowest detectable number of EPCs in this model is approximately 1x106.

WP13 Molecular imaging of NF-ĸB activation and imaging chronic inflammation using optical probes

P43: • Establishing NF-B reporting prostate cancer cells (PC-3) and performing in vivo imaging studies

jointly (jointly with P11). • Has jointly with P11 worked with phytochemicals and effect on NF-B activity in intestine. • Has contributed with animal model (NF-B luciferase) jointly with P2 and P17b for the

atherosclerosis project described in D13.21.

P2: • Jointly with P17b, P2 has performed PET-imaging studies in mice subjected to atherosclerosis

P11: • Establishing NF-B reporting prostate cancer cells (PC-3) and performing in vivo imaging studies

jointly (jointly with P43) • Testing inhibitory effect of dietary nutrients with emphasis on coffee and effect in the intestine in

NF-B luciferase model animal models using luciferase as a reporter for NF-B activity • Has contributed with experiments on NF-B luciferase model for the atherosclerosis project

described in D13.21 • Has contributed with lentiviral construct for NF-B luciferase transfections in B16 melanoma cells

and comments.

P15b: • No contribution in this reporting period

P17b: • Extensive experiments have been done in a model of atherosclerosis using both ex vivo optical

imaging of aorta (NF-B luciferase) and PBR imaging using the probe F18-FEDAA1106 to elucidate role of signalling pathways.



P37b: • P37b has contributed with comments and advice regarding development of prostate cancer model

P40b: • No contribution in this reporting period

AP02: • AP02 has made different versions of redox sensitive fluorescent proteins, which have been tested

in vitro in B16 melanoma cells. In vivo imaging experiments have been carried out, but detection of signal failed, possibly due to choice of transfection method.

WP14 Integrating Activities

P1: To foster internal (inside the network) and external (with scientists from outside the network) exchange Partner 1 organised the main two DiMI and ESMI conferences during this project period: 1) 4th European Molecular Imaging Meeting – EMIM on May 27-30, 2009 in Barcelona, Spain, including the 4th DiMI annual meeting, 2) 5th European Molecular Imaging Meeting on May 26-29, 2010 in Warsaw, Poland, including the 5th DiMI annual meeting. Furthermore, P1 contributed to the participation in some other conferences to enhance the world wide visibility of DiMI and ESMI, i.e. World Molecular Imaging Congress, 23-26 September 2009 in Montreal, Canada; the congress of the European Association for Nuclear Medicine – EANM, 10-14 October 2009 in Barcelona, Spain; the World Molecular Imaging Congress, 8-11 September 2010 in Kyoto, Japan as well as the EANM Congress 2010, 9-13 October 2010 in Vienna, Austria. Additionally the DiMI and ESMI websites were enhanced to facilitate communication and integration. The web-based formula for the measurement of integration activities was updated in the DiMI intranet to facilitate the partners’ reporting of integration activities.

P12d: The INSTN coordinated the overall DiMI training activities with the aim of spreading the knowledge and know-how between the scientists in the field of molecular imaging as well as to enhance their collaborations. Therefore, once a year, a leaflet announcing the overall training activities was conceived and produced by partner 12d for dissemination purpose. Those leaflets were diffused at several conferences/schools/events. DiMI training activities have also been announced on several web sites (like DiMI, ESMI, EMMI) and diffused throughout an extensive email list of laboratories working in the molecular imaging field.

P13: Partner 13 supported the European Society of Molecular Imaging and also participated actively in the organization of the meetings. P13 participated to the organization and/or to the animation of several DiMI training and workshop events (among others, Optical Imaging in Small Animals in Leiden, DiMI workshop; Molecular Imaging for Drug Discovery, Milan, DiMI workshop; Multimodal Imaging of Stem Cell Trafficking, Cologne, DiMI Training course). In addition, P13 has promoted the network in the framework of 10 major international conferences and three national conferences and imaging workshops.

WP15.1 Activities of the Board for Training (BOT)

P12a: Coordination and scientific administration of the European Master programme in Molecular Imaging, TOPIM workshop, International School in Imaging. Design of the two Intensive Programmes on “PET imaging” and “Molecular Imaging and industrial context, state of the art, multimodal imaging”. P12a sent 10 lecturers to those IPs.

P1: Coordination and Management of the International school on Imaging, dissemination of the overall training activities proposed within DiMI. All DiMI trainings courses have been announced through the mailing list and the DiMI websites as well as trough dissemination of print material. Additionally the EMMI master programme and more MI trainings courses have been announced through the various dissemination channels. P1 sent two lecturers to both EMMI Intensive Programmes “PET imaging”, which took place on


May 25–June 5 2009 and April 12-23 2010 in Saclay, France Furthermore P1 sent one lecturer to the EMMI Intensive Programmes “Molecular Imaging and industrial context, state of the art, multimodal imaging”, which took place on December 7–18 2009 in Saclay, France

P2: Delivery of the course “MicroPET and microPET/MR Imaging Science” November 9 – 13, 2009

P3: Organization of the medium term course “Synthesis, physico-chemical characterisation and assessment of Lanthanide-based MRI probes for cellular labelling”. September 14–18, 2009. Management of the Intensive Programme dedicated to “Design and validation of imaging probes”. Coordination and scientific administration of the European Master programme in Molecular Imaging in Turin. P3 sent one lecturer to the IP “Molecular Imaging and industrial context, state of the art, multimodal imaging”, which took place on December 7–18 2009 in Saclay, France.

P4a: Organization of two courses on “PET and SPECT radiopharmaceuticals preparation: design, radiolabelling strategy and radiosynthesis” November 2–5, 2009 and “PET and SPECT radiopharmaceuticals preparation: GMP, regulatory aspects and prerequisite for human applications” November 2–5, 2009.

P5: Organization of two courses: “Experimental models of brain ischemia” November 9-13, 2009 and “In vitro models as tools for the study of neurological diseases” March 11-12, 2010

P6 (additionally): Organization of two workshops on “Molecular Imaging in Drug Discovery and Preclinical Development - a training course in molecular imaging” on June 22-23, 2009 and June 21-22, 2010.

P7: Organization of the course “Basic kinetic Modeling in Molecular Imaging” medium term training. Testing, validation and implementation of new computer exercises on February 1–5, 2010.

P8: Organization of a course on “Microscopical research techniques in biomedical applications” Management of Intensive Programme dedicated to “NeuroMRI” and “FELASA – Certificate for Animal Experimentation”. Coordination and scientific administration of the European Master programme in Molecular Imaging in Antwerp, Belgium. Organization of a medium term course on “Microscopical research techniques in biomedical applications”, March 8-12, 2010. P8 sent one lecturer “Molecular Imaging and industrial context, state of the art, multimodal imaging”, which took place on December 7–18 2009 in Saclay, France, and one lecturer to the IP PET imaging which took place on May 25 – June 5 2009 and April 12-23 2010 in Saclay, France.

P10: Organization of a course on “Molecular imaging in cardiology and oncology” May 5–8, 2009.

P12d: Coordination, management and final assessment of the overall short/medium trainings and European Master in Molecular Imaging at the INSTN. Management of two Intensive Programmes with Partner 12a: “PET Imaging” and “Molecular Imaging and industrial context, state of the art, multimodal imaging” Submission of applications for Erasmus Mundus and Accompanying measures programmes

P40a: Became new partner of the EMMI Intensive Programmes “PET imaging” and “Molecular Imaging and industrial context, state of the art, multimodal imaging” and sent two lecturers to the EMMI Intensive Programmes “Molecular Imaging and industrial context, state of the art, multimodal imaging”, which took place on December 7–18 2009 in Saclay, France.



WP15.2 Activities of the Board for Dissemination and Communication (BODIC)

P12a: Activities concerning dissemination during this period focused on the public relations for the Hot Topics in Imaging (TOPIM) workshop 2010 as well as on activities for the European Society for Molecular Imaging – ESMI including the promotion of the 4th European Molecular Imaging Meeting on 27-30 May in Barcelona, Spain.

P1: Major activities of Partner 1 concerned the dissemination activities for the network like DiMI publications brochure No. 3+4, announcements of events and DiMI trainings, quarterly publication of the DiMI newsletter, and design of new ESMI dissemination material and DiMI training posters as well as the maintenance and further development of the DiMI and ESMI webpages. The main focus of this period’s work lay on the public relations activities for the EMIM 2009, 2010 and 2011 as well as for TOPIM 2010 and 2011.

P3: Prof. Silvio Aime and his team were local organizers of the DiMI Winter School 2010 “Hot Topics in Molecular Imaging – Imaging and Systems Biology”. This TOPIM workshop took place on 7-12 February in Bardonecchia, Italy.

P5: Prof. Anna Planas and her team were local organizers of the 4th European Molecular Imaging Meeting 2009 including the 5th DiMI annual meeting. This meeting took place on 27-30 May in Barcelona, Spain.

P37b: Prof. Clemens Lowik was elected president of the ESMI in May 2010. He and his team are the local organizers of the 6th European Molecular Imaging Meeting 2011 taking place on June 19-21 in Leiden, The Netherlands. Overall organization and management of this meeting had already started in close collaboration between P1 and P37b.

P51: Prof. Renata Mikolajczak and her team were local organizers of the 5th European Molecular Imaging Meeting – EMIM in Warsaw, Poland. The EMIm 2010 took place from May 16 to May 29, 2010. The 5th EMIM was also the final DiMI meeting.

WP16 Management Activities

P1:

The management of the DiMI network is performed by the DiMI Management Office (MO). The MO comprises the project coordinator (Prof. Dr. Andreas Jacobs), the financial manager (Irene Simon), the project manager (Heike Brucherseifer), the web content manager (Dr. Sabine Stötzer) as well as the public affairs manager (Doris Kracht). The MO is responsible for the overall legal, contractual, ethical and financial management tasks. The MO arranged all necessary DiMI network meetings, prepared the necessary amendments (budget amendment, change of legal details of one partner) to the contract, prepared the reporting for the network and was responsible for the calculation and allocation of the DiMI budget. The overall day-to-day communication within the network and outside the network was arranged by the management office, the continuous maintenance of the DiMI webpage as well as the intensified efforts for public visibility. The communication with the European Commission was intensified during the whole reporting period in order to establish close cooperation.

SMB: The other partners of the work package are members of the DiMI Scientific Management Board. This includes the partner P2, P3, P4a, P5, P6, P7, P8, P9a, P10, P11, P12a, and P13. The regular meetings and communication between the SMB and the coordinator assure the efficient internal and external communication within DiMI. The 13 members of the DiMI SMB meet on a regular bi-monthly basis during conference calls, this period six calls including a scientific think-tank and one meeting during the annual meeting in Leuven June 2008. During these meetings important decisions concerning the network are taken, information exchanged and also new developments are being discussed. All meeting minutes are available to the SMB and the GB members via DiMI intranet.


II. Explanatory note on any major cost item

P1

Major costs of Partner P1 concerned the operation of the management office and the related personnel costs. Additionally the MO had costs for conference calls, audit certificate, print material, office supplies, and website support. Also the organisation of DiMI networking events (Annual Meeting, Joint WP Meeting, ESMI conference) was a major cost item. Further costs for P1 related to scientific personnel costs pursuing the research, their travel costs to take part in group meetings, annual meeting and training courses.

P2

Major costs for the project continue to be installation and commissioning the split magnet system in the West Forvie preclinical facility. The overall objective of the later stages of this project has been to transform the original feasibility study of a split magnet based PET/MR scanner into a system suitable for serial studies. A series of failures of equipment has delay the project but now initial tests have been completed and confirm an improvement in the underlying resolution of the PET scanner. This is an extremely complex system involving components from three different manufactures as well as specialised additions developed at the University of Cambridge. Notably there are no other preclinical systems available world wide yet and it is now anticipated that this scanner will commence studies in the first quarter of 2011.

P3

Major cost in the reporting period was related to the salary of the personnel (1 post-doc and 1 PhD student) supported by the project plus own research staff. Other costs were due to travel expenses, and the organization of the course on “Synthesis, physico-chemical characterization and assessment of lanthanide-based MR imaging probes for cellular labeling” held in Torino in October 2009 in association with the EMMI intensive course.

P4

The main cost items deal with: chemical materials, radioisotopes, material for pharmacological experiments (drugs, isotopes, film, and animals), recycling wastes, salary for a biologist and travel for meetings. The main resources used deal with: chemistry and radiochemistry; Development, characterization and biological evaluation of new radioligands; Personnel for Pharmacological studies; Participation in congresses.

P5

Major costs were for this report were in personnel (main task in participation and organisation of the training platform) and we had some expenses related to the organisation of the training courses (we organised two separate courses). We had travelling expenses as we had a student doing some experiments in another DiMI laboratory, and travelling to attend DiMI meetings. Finally we bought some laboratory consumables.

P6

The main cost items deal with: Scientific personnel, personnel training, disposables, consumables, kit for bioluminescence, kit for PCR, reagents for molecular biology and cell culture, mice, cost for mice maintenance, travel: Personnel € 62.967,86 Travel € 6.589,31 Consumables and mice € 23.055,36 People involved were:



Adriana Maggi, professor; Elisabetta Vegeto and Paolo Ciana, research; Sara Della Torre and Gianpaolo Rando, post-doc; Giuseppina Monteleone and Valeria Benedusi, doctoral student, Elisa Faggiani and Clara Meda, technicians; Isabella Rotondo and Rossana Notarantonio, scientific secretary and administration.

P7

Major costs for the project were related to scientific personnel, software licenses, travel expenses for the DiMI annual meeting as well as meetings with partners and training platforms.

P8

Costs covered by DiMI: Major cost item was the salary of postdoc researcher Greetje Vanhoutte. Other cost was the purchase of consumables and anaesthesia for the experiments and for organising the DiMI-training 2009. Also cost for MRI-measuring time was partly charged on the project.

Additional costs (not covered by DiMI): This mainly consists of cost for labour (the personnel cost). Other cost was to cover (the rest of) the MRI measuring time, animal housing and animal care, two of the major cost items. Other cost also includes purchase of anaesthesia, inhalation gasses, the cost for the DiMI-training 2010 and travel cost (DiMI Joint WP meeting from 25-26 March 2010 in Münster, Germany).

P9

P09a: Major costs for the project DIMI on the reporting period 01/04/09 to 30/09/10 were related to scientific personnel (permanent researchers). The other costs helped purchasing consumables (lab ware). A small part was dedicated to travel expenses to the congress ISMRM (presentation of DIMI drugs) and to the congress ESMI (presentation of DIMI results). P09b: Major costs for the project have been related to consumables for tumour models (cell culture, cost and handling of research animals), contrast probe marking (antibodies) and ultrasound imaging (anaesthesia). Scientific personnel (Graduate researcher) have also been partially financed. Some costs are related to preparation of specimens for ex-vivo studies, fabrication of posters for scientific presentations and travel expenses (to the DiMI annual Meeting and another forum on small animal ultrasonic imaging and molecular imaging techniques). The final 6 months major costs were centred on costs for attending the annual meeting in Warsaw.

P10

Major costs for the project were related to scientific personnel pursuing the proposed experiments; travel expenses (some personnel costs appear as travel costs, because Dr. Antti Saraste who was not permanently employed in Munich had to make several trips to Munich to carry out the experiments; thus the TTP position was open); consumables (reagents, lab ware); and research animals.

P11

Major cost for the project were related to scientific personnel (postdoc, doctoral students) pursuing the proposed experiments; to cover travel expenses to DiMI related Meetings, to purchase consumables (reagents, labware). The largest expense relates to housing and handling research animals.

P12

For the fifth period, major cost for the project were related to scientific and teaching personnel from SHFJ (P12a), MIRCen (P12b) and INSTN (P12d). This includes:

- the payment of a fixed-term contract for a young researcher at the SHFJ - the time spent on the research projects and the organisation of DiMI training by the

researchers, the training managers and the technical staff - the expenses related to the participation of the scientific personnel to international congresses


These expenses allowed Partner 12 to pursue the scientific projects initiated in the frame of DiMI, to improve the trainings, and present the scientific data at international congresses. No major equipment purchases were done.

P13

Human resources were mainly dedicated: To test of the 3D Real-Time Optical module. Due to non availability of the system and animal models at the same time, some experiments have been done with off-DIMI partner. A lot of effort was put on the algorithmic and post processing software. Some expenses have been included related to the EMIM conference in Warsaw.

P14

For partner 14a, about 40% of the budget was spent to animal costs, the rest was used for consumables for histology, molecular biology and cell culture. For partner 14b main cost items were animal purchase, housing, handling and microPET imaging.

P15

The main expenses have been: animals and chemicals. Some travel expenses in connection to the final consortium meeting.

P17

The costs by 17b included purchase and maintenance of wild-type C57BL/6 mice. To assess whether genetic deletion of JNK1 or MKP-1 alters vascular physiology we studied JNK1 knockout and MKP-1 knockout mice. Funding was used to maintain colonies of JNK1-/-, MKP-1-/- mice to provide animals for this study. The study also required purchase of isofluorane to anaesthetize mice, analgesia, 18F-FDG, 18F-FEDAA and fluorescent antibodies. Funding was also required to carry out PET imaging (charged at an hourly rate by the Biological Imaging Centre, Imperial College London). The remainder will be used for travel expenses and accommodation for attending the DiMI meetings.

P18

Major costs for the project were related to purchase animals for the experiments (APOE- and control mice) and the necessary consumables. Other expenses include travel and lodging to attend international meetings and congresses where the results of the project have been presented and discussed with other groups.

P20

All costs were travel to and subsistence at DiMI related meetings.

P21

Major cost items for the project were consumables (mainly cell culture reagents and labware, reagents for molecular biology) and animals for experiments; travel costs incurred to meet and exchange with collaborating groups.

P22

Major cost for the project were related to scientific personnel (post-doc, doctoral students) pursuing the proposed experiments; to cover travel expenses to the DiMI Annual Meeting, to purchase consumables (reagents, lab ware). The largest expense relates to housing and handling research animals.

P24

Partners account is run at P1 KUK, P24 has been inactive during this period; only travel costs have been paid



P25

A large fraction of the costs was dedicated to personnel to assure performance of the proposed scientific projects. Consumables costs were spent predominantly on cell culture materials and cell-specific antibodies for (stem) cell characterization of cell cultures or on brain tissue sections. Travel costs were used for participation at various DiMI and ESMI meetings.

P26

Salary € 16.782 PhD-Student has worked on the detection of atherosclerotic plaque instability, both in animal models of disease as in patients with carotid artery stenosis. He also did the compilation of data collected and acquired in JPA1-4. The PhD-student has worked in the period 01.04.2009 till 31.03.2010 4,8 person months for the project. Planned were 6 person months. Our University is willing to pay for the overspending out of our own. There are no costs made for materials, only for the audit certificate € 1.220 and adjustments previous periods - € 529.

P27

The main costs were material for building an optical unit for consecutive as well as simultaneous MRI/bioluminescence measurements. Other minor costs were for a national educational course in molecular imaging as well as travelling for exchange of information within and adjunct to the network of molecular imaging.

P29

Consumables (reagents, labcost) Travel cost for DiMi meetings and EANM Prof Leenders declared salary for PhD-student: Anna Bartels

P31

No major cost items were planned during the period. Minor cost items included the purchase of materials for western blotting and antibodies out of own funds. Work in addition to AC own staff was performed by postgraduate students under direct supervision.

P32

Major cost for the project are related to scientific personnel (professor, assistant professors, doctoral students) pursuing the proposed experiments; to cover travel expenses to the DiMI Annual Meeting, to purchase consumables).

P33

Scientific personnel pursuing data analysis and writing scientific articles, travel expenses to the DIMI annual meeting, consumables, radiochemistry products

P34

No major cost items or major deviations from budget have incurred. No personnel cost. Consumables for viral vector production and Audit Certificate cost.

P35

The major costs for the project were associated with partial support for a post-doctoral assistant and for 2 PhD students who pursued the experiments discussed in the scientific report.

P36

The major costs incurred in the last reporting period are referred to Personnel costs for 7.472,43 Euro (Valentina Garibotto, 1 Pm, April 2009 - Ilaria Tafi, 4 Pm, June 2009 - September 2009), Travel costs for 6.270,45 Euro (Perani Daniela, Cappa Stefano to Seattle, Florea Ioanna e Cristina Monterisi to


Barcellona, Valentina Garibotto to Firenze, adjustment to the previous year) and the cost of the audit certificate for an amount of 1.560 Euro.

P37

37a: The focus has been on cell tracing with MRI. Major cost items consist of personnel costs for the technician fully appointed for this project, consumables etc necessary to perform the work. A minor part of the DiMI budget has been spent on shipment costs. P37b work focused on the construction and generation of expression and lentiviral vectors with multimodal reporter genes for bioluminescence, fluorescence and MR. Evaluation of these constructs and genetically engineering of various cell lines. Cost items and resources: Transport of animals and animal housing, anaesthetics, use MRI and OI camera, use substrates (luciferine), consumables for cell culture - vector production, optical probes, travel expenses, registration costs congresses and printing costs for scientific posters.

P39

We had expenses for three major items: (1) Acquisition of small equipment, essentially for neuroimaging analysis, to contribute to exchanges on multivariate data analyses (2) Travel expenses for scientific personnel, PhD student and researchers, to contribute to exchange of information linked to our DIMI project (3) Expenses for DIMI related publications

P40

The DiMI money was mainly spent on funding research personnel that was involved in projects related to the network of excellence. Moreover travelling costs were reimbursed that allow us to more closely cooperate with the different DiMI groups and / or present DiMI related research result in relevant meetings. Finally consumables necessary for the projects were purchased through DiMI funds.

P42

The main cost items deal with kits for molecular biology, chemistry, purchase of animals and animal housing.

P43

The major costs for the experiments done in the last period are related to personnel costs, housing research animals, luciferase substrate (luciferin). In addition we have had costs related licensing fees of transgenic reporter mice.

P45

The total amount of costs incurred by the University of Navarra for the DiMI project in this period are 3431.98 Euros. There are not Personnel Costs, because the IP and his team are actually working in the US. There is a 47.98% of the budget spent in their travels to the ESMI meeting. A 42,4% of the budget is for the audit certificate, and the rest of the budget is over heads..

P47

Partners account is run at P1 KUK

P48

Not active in this period



P50

For this period all consumables, about 3 000 Euro, were paid from university and other sources. Thus, sum of 10 220 Euro was spent for parts of salaries of three PhD students (Polasek, Simecek and Strnadova).Travel cost 556 Euro – travelling to Muenster, DiMI meeting.

P51

Major cost for the project were related to scientific personnel (doctoral students) pursuing the proposed experiments; to cover travel expenses to the DiMI Annual Meeting, to purchase consumables (reagents, lab ware) and to travel to collaborating PET laboratory in Poland.

P52

In addition to our own resources, DiMI funds were used to pay the personnel costs (4.5 person months) of a PhD student working on the project, to cover travel expenses to the 2009 DIMI annual meeting and ESMI Congress in Barcelona, to the 2010 WP10 meeting in Münster, and to DiMI training workshops in Barcelona (2009), Cologne (2009) and Antwerp (2010).

P53

Major cost items were travel expenses (DiMI meetings and workshops), consumables required for animal costs and optical bioluminescent imaging and personnel (students working on the project).

P54

Payroll costs for Stephen Carter (April 2009 to January 2010) Travel and expenses of project staff at NRM conference, Glasgow (July 2010) Venue costs, speaker travel and accommodation for WMIC radiochemistry symposium, Manchester (July 2010) Conference in Minneapolis attended by Stephen Carter, Minneapolis (June 2009) METPET meeting, Copenhagen (June 2009) DiMI meeting, Munster (March 2010) BNSO meeting, Glasgow (June 2009) European Molecular Imaging Meeting, Warsaw (May 2010)

P55

Major costs for the project were related to cover travel expenses.

P56

The budget has been spent for consumables.


III. A tabular overview of budgeted costs and actual costs (simplified)

PARTICIPANTS TYPE of

EXPENDITURE (excl. overheads)

Plan Period 5 (JPA5)

Actual Costs Period 5 (EUR)*

Pct. spent Remaining BudgetPeriod 5 (EUR)

Period 5 Year 5

e2 b1 b1/e2 e2-b1

P1 – KUK Total Person-month 75 83 111% -8

incl. FlexiFunds + Personnel costs 384.750 425.790 111% -41.040

shared expenses Other costs ('the rest') 115.800 79.000 68% 36.800

Total Costs 500.550 504.790 1,0 -4.240

P2 – UCAM-WBIC Total Person-month 77 49 64% 28

Personnel costs 283.360 180.320 64% 103.040

Other costs ('the rest') 122.400 20.613 17% 101.787

Total Costs 405.760 200.933 0,5 204.827

P3 – UniTo Total Person-month 102 102 100% 0

Personnel costs 375.360 375.360 100% 0

Other costs ('the rest') 123.000 123.000 100% 0

Total Costs 498.360 498.360 1,0 0

P4 – UnivTours Total Person-month 37 33 90% 4

P04a+P04b Personnel costs 177.390 158.213 89% 19.177


Total Costs 324.390 305.213 0,9 19.177

P5 – IDIBAPS Total Person-month 63 63 100% 0

Personnel costs 262.710 253.680 97% 9.030

Other costs ('the rest') 103.200 112.706 109% -9.506

Total Costs 365.910 366.386 1,0 -476

P6 – UNIMI Total Person-month 56 56 100% 0

Personnel costs 206.080 206.080 100% 0


Total Costs 296.580 296.580 1,0 0

P7 – RH-NRU Total Person-month 74 74 100% 0

Personnel costs 333.000 397.315 119% -64.315


Total Costs 412.500 529.753 1,3 -117.253

P8 – UA-imaging Total Person-month 92 92 100% 0

Personnel costs 448.040 394.357 88% 53.683


Total Costs 490.340 444.562 0,9 45.778

P9 – CNRS Total Person-month 57 57 100% 0

P09a+P09b Personnel costs 221.160 221.160 100% 0


Total Costs 334.160 232.892 0,7 101.268

P10 – NUK_TUM Total Person-month 72 60 83% 12

Personnel costs 369.360 260.912 71% 108.448


Total Costs 530.960 299.932 0,6 231.028

P11 – UiO Total Person-month 48 37 77% 11

Personnel costs 257.760 198.690 77% 59.070


Total Costs 312.560 240.932 0,8 71.628

P12 – CEA Total Person-month 47 20 43% 27

P12a+P12b+P12d Personnel costs 213.900 95.914 45% 117.986


Total Costs 339.900 130.138 0,4 209.762








Period 5 Year 5

e2 b1 b1/e2 e2-b1

P13 – BIOSPACE Total Person-month 10 13 130% -3

Personnel costs 52.800 67.557 128% -14.757


Total Costs 59.800 80.828 1,4 -21.028

P14 – KULRD/LMIRC Total Person-month 185 185 100% 0



Total Costs 1.128.950 961.116 0,9 167.834

P15 – ULUND Total Person-month 33 33 100% 0



Total Costs 230.740 101.478 0,4 129.262

P17 – ICL Total Person-month 9 8 89% 1



Total Costs 55.120 66.599 1,2 -11.479

P18 – HSP Total Person-month 3 3 100% 0

Personnel costs 12.510 12.510 100% 0


Total Costs 14.510 15.610 1,1 -1.100

P20 – SHEFC Total Person-month 3 3 100% 0

Personnel costs 11.040 11.040 100% 0


Total Costs 12.040 24.657 2,0 -12.617

P21 – UKB Total Person-month 37 37 100% 0

Personnel costs 189.810 189.810 100% 0


Total Costs 231.810 233.293 1,0 -1.483

P22 – KI Total Person-month 58 58 100% 0



Total Costs 384.240 384.240 1,0 0

P24 – FZJ Total Person-month 0 0 #DIV/0! 0

Personnel costs 0 0 #DIV/0! 0

Other costs ('the rest') 0 0 #DIV/0! 0

Total Costs 0 0 #DIV/0! 0

P25 – MPIFNF Total Person-month 48 60 125% -12

Personnel costs 246.240 300.000 122% -53.760


Total Costs 299.240 375.000 1,3 -75.760

P26 – CARIM Total Person-month 6 7 117% -1

Personnel costs 34.560 30.548 88% 4.012

Other costs ('the rest') 2.000 691 35% 1.309

Total Costs 36.560 31.239 0,9 5.321

P27 – CBI Total Person-month 12 12 100% 0

Personnel costs 57.360 57.360 100% 0


Total Costs 67.360 67.360 1,0 0

P29 – Uni. Gro./PET Total Person-month 6 6 100% 0

P29b Personnel costs 34.560 34.560 100% 0


Total Costs 71.560 71.560 1,0 0







Period 5 Year 5

e2 b1 b1/e2 e2-b1

P31 – UNEW Total Person-month 35 25 71% 10

Personnel costs 128.800 103.250 80% 25.550


Total Costs 181.800 159.287 0,9 22.513

P32 – TU/e Total Person-month 115 115 100% 0

Personnel costs 662.400 662.400 100% 0


Total Costs 759.400 675.124 0,9 84.276

P33 – CNR-IBB Total Person-month 10 9 90% 1

Personnel costs 36.800 36.781 100% 19


Total Costs 42.800 46.681 1,1 -3.881

P34 – FTELE.IGM Total Person-month 20 14 70% 6

Personnel costs 73.600 51.520 70% 22.080

Other costs ('the rest') 11.000 11.977 109% -977

Total Costs 84.600 63.497 0,8 21.103

P35 – DUR Total Person-month 78 93 119% -15

Personnel costs 287.040 306.511 107% -19.471

Other costs ('the rest') 78.000 78.199 100% -199

Total Costs 365.040 384.710 1,1 -19.670

P36 – UVita-P Total Person-month 40 40 100% 0

Personnel costs 147.200 147.200 100% 0

Other costs ('the rest') 0 8.153 #DIV/0! -8.153

Total Costs 147.200 155.353 1,1 -8.153

P37 – LUMC Total Person-month 74 74 100% 0

P37a+P37b Personnel costs 426.240 466.671 109% -40.431


Total Costs 498.240 526.829 1,1 -28.589

P39 – ULG Total Person-month 4 4 100% 0

Personnel costs 19.480 19.480 100% 0


Total Costs 27.480 27.480 1,0 0

P40 – UKM Total Person-month 127 127 100% 0



Total Costs 762.510 762.510 1,0 0

P42 – CYCERON Total Person-month 51 51 100% 0

Personnel costs 247.860 247.860 100% 0


Total Costs 295.860 295.860 1,0 0

P43 – CGENE Total Person-month 9 9 100% 0

Personnel costs 48.330 48.330 100% 0


Total Costs 53.330 53.330 1,0 0

P45 – UNAV Total Person-month 3 3 100% 0

Personnel costs 12.510 12.510 100% 0

Other costs ('the rest') 0 3.432 #DIV/0! -3.432

Total Costs 12.510 15.942 1,3 -3.432

P47 – Cyclopharma Total Person-month 0 0 #DIV/0! 0











Period 5 Year 5

e2 b1 b1/e2 e2-b1

P48 – MEDRES Total Person-month 0 0 #DIV/0! 0




P50 – Charles U. Total Person-month 21 21 100% 0

Personnel costs 21.000 21.000 100% 0


Total Costs 46.000 46.000 1,0 0

P51 – POLATOM Total Person-month 3 3 100% 0

Personnel costs 3.000 3.000 100% 0


Total Costs 40.000 40.000 1,0 0

P52 – IEM ASCR Total Person-month 16 16 100% 0

Personnel costs 16.000 18.515 116% -2.515


Total Costs 46.000 45.206 1,0 794

P53 – KUR Total Person-month 24 24 100% 0

Personnel costs 123.120 123.120 100% 0


Total Costs 167.120 167.120 1,0 0

P54 – UNIMAN Total Person-month 30 50 167% -20

Personnel costs 110.400 184.000 167% -73.600


Total Costs 133.400 213.441 1,6 -80.041

P55 – Vumc Total Person-month 14 14 100% 0

Personnel costs 80.640 93.398 116% -12.758


Total Costs 134.640 112.712 0,8 21.928

P56 – UE Total Person-month 27 27 100% 0

Personnel costs 138.510 138.510 100% 0


Total Costs 163.510 163.510 1,0 0

TOTAL Total Person-month 1.910 1.870 98% 40

Personnel costs 8.775.240 8.391.029 96% 384.211

Other costs ('the rest') 2.590.100 2.027.015 78% 563.085

Total Costs 11.365.340 10.418.044 0,9 947.296


IV. A tabular overview of budgeted person months and actual person months, by contractor and by work package

WP01 Ultra high cerebral and heart imaging and quantitation with Single- Actual PM 10 0 10

Planned PM 9 0 9WP02 Quantitative microPET and multi-modality (PET/MR, OT/MR) scanner Actual PM 0 43 43

Planned PM 0 52 52WP03 Development of radiopharmaceutical probes for neurodegeneration Actual PM 9 75 84

Planned PM 11 75 86WP04.1 Development of library of innovative MRI probes and improved Actual PM 9 98 107

Planned PM 53 50 103WP04.2 Development of optical and combined imaging probes Actual PM 28 83 111

Planned PM 32 67 99WP05 Animal library for diagnostic molecular imaging in neuroscience and Actual PM 18 228 246

Planned PM 12 239 251WP06 Evaluation of the role of estrogen receptors in a mouse model of Actual PM 20 6 26

Planned PM 20 6 26WP07 Non-invasive phenotyping of animal models for neurodegenerative Actual PM 10 88 97

Planned PM 8 99 107WP08.2 Early diagnosis of neurodegenerative disease Actual PM 25 94 119

Planned PM 20 104 122WP09 Neuroinflammation Actual PM 7 131 138

Planned PM 8 126 134WP10 Stem cell trafficking in the CNS Actual PM 19 184 203

Planned PM 23 174 197WP11.1 Multimodality characterization of atherosclerotic plaques Actual PM 17 188 204

Planned PM 21 201 222WP11.2 Characterization of myocardial angiogenesis Actual PM 18 95 112

Planned PM 7 99 106WP12 Cardiac stem cell therapy monitored by molecular imaging Actual PM 36 74 110

Planned PM 38 72 110WP13 Molecular imaging of NF-ĸB activation and imaging chronic Actual PM 24 29 53

Planned PM 20 31 51WP14 Integrating activities Actual PM 7 1 8

Planned PM 7 0 7WP15.1 Activities of the Board for Training (BOT) Actual PM 14 17 30

Planned PM 17 17 33WP15.2 Activities of the Board for Dissemination and Communication (BODIC) Actual PM 17 5 22

Planned PM 16 5 21WP16 Management activities Actual PM 23 9 32

Planned PM 23 7 30TTP DiMI Training Platforms Actual PM 75 43 117

Planned PM 80 65 144

Actual PM 381 1488 1868

Planned PM 424 1488 1910

Per

son

Mo

nth

s T

ota

Total Project Person Months (all)

Total Project Person Months (all)

To

tal D

iMI p

aid

To

tal A

C o

wn



Totals

P01

P02

P03

P04a

P04b

P05

P06

P07

P08

P09a

P09b

P10

P11

P12a

P12b

P12d

P13

P14a

P14b

P15a

P15b

P17a

P17b

P20

P21

P22a

P22b

P25

P26

P27

P29b

P31

P32

P33

P34

P35

P36

P37a

P37b

P39

P40a

P40b

P42

P43

P45

P48

P50

P51

P52

P53

P54

P55

P56

Actu

al P

M10

10

Plan

ned

PM9

27

Actu

al P

M

Plan

ned

PM

Actu

al P

M9

23

13

Plan

ned

PM11

83

Actu

al P

M9

51

2,5

Plan

ned

PM53

53

Actu

al P

M28

112

15

Plan

ned

PM32

1715

Actu

al P

M18

43

14

33

Plan

ned

PM12

41

43

Actu

al P

M20

20

Plan

ned

PM20

20

Actu

al P

M10

63

0,5

Plan

ned

PM8

62

Actu

al P

M25

6,5

44

37

Plan

ned

PM20

74

36

Actu

al P

M7

52

Plan

ned

PM8

62

Actu

al P

M19

42

62

4,5

0,5

Plan

ned

PM23

41

126

Actu

al P

M17

1,5

39

3

Plan

ned

PM21

183

Actu

al P

M18

412

2

Plan

ned

PM7

43

Actu

al P

M36

36

Plan

ned

PM38

236

Actu

al P

M24

0,5

104

9

Plan

ned

PM20

110

9

Actu

al P

M7

40,

52

Plan

ned

PM7

41

2

Actu

al P

M14

45

10,

53

Plan

ned

PM17

45

11,

55

Actu

al P

M17

152

Plan

ned

PM16

122

2

Actu

al P

M23

211

1

Plan

ned

PM23

181

11

11

Actu

al P

M75

712

412

64

4,5

121

12

Plan

ned

PM80

712

86

124,

512

612

Act

ual P

M38

171

1410

20

2027

126

534

1211

142

413

00

00

04

00

00

49

50

00

39

015

59

00

30

09

015

35

110

00

Plan

ned

PM42

466

3289

00

027

126

534

016

2912

610

00

00

00

00

00

09

60

00

010

00

50

00

00

09

015

30

06

00

Tota

l Pro

ject

Per

son

Mon

ths

(DiM

I fun

ded)

Par

tner

Per

son

Mo

nth

s p

er W

ork

pac

kag

e (D

iMI

fun

ded

)

Ultr

a hi

gh c

ereb

ral a

nd h

eart

imag

ing

and

quan

titat

ion

with

Sin

gle-

Phot

on e

mitt

ers

Qua

ntita

tive

mic

roPE

T an

d m

ulti-

mod

ality

(PET

/MR

, OT/

MR

) sca

nner

de

velo

pmen

t

Dev

elop

men

t of r

adio

phar

mac

eutic

al p

robe

s fo

r neu

rode

gene

ratio

n di

seas

es

DiM

I Tra

inin

g Pl

atfo

rms

WP0

1

WP0

2

WP0

3

WP0

4.1

WP0

4.2

Neu

roin

flam

mat

ion

Stem

cel

l tra

ffick

ing

in th

e C

NS

Mul

timod

ality

cha

ract

eriz

atio

n of

ath

eros

cler

otic

pla

ques

Dev

elop

men

t of l

ibra

ry o

f inn

ovat

ive

MR

I pro

bes

and

impr

oved

m

etho

ds fo

r “in

viv

o” c

ellu

lar l

abel

ling

Dev

elop

men

t of o

ptic

al a

nd c

ombi

ned

imag

ing

prob

es

Inte

grat

ing

activ

ities

Activ

ities

of t

he B

oard

for T

rain

ing

(BO

T)

Activ

ities

of t

he B

oard

for D

isse

min

atio

n an

d C

omm

unic

atio

n (B

OD

IC)

Man

agem

ent a

ctiv

ities

WP1

5.2

WP1

6

Cha

ract

eriz

atio

n of

myo

card

ial a

ngio

gene

sis

Car

diac

ste

m c

ell t

hera

py m

onito

red

by m

olec

ular

imag

ing

Mol

ecul

ar im

agin

g of

NF-ĸB

act

ivat

ion

and

imag

ing

chro

nic

infla

mm

atio

n us

ing

optic

al p

robe

s

WP0

5

WP0

6

WP0

7

WP0

8.2

WP0

9

Anim

al li

brar

y fo

r dia

gnos

tic m

olec

ular

imag

ing

in n

euro

scie

nce

and

card

iova

scul

ar

Eval

uatio

n of

the

role

of e

stro

gen

rece

ptor

s in

a m

ouse

mod

el o

f Al

zhei

mer

’s d

isea

se a

nd g

ener

atio

n of

nov

el re

porte

r sys

tem

s

Non

-inva

sive

phe

noty

ping

of a

nim

al m

odel

s fo

r neu

rode

gene

rativ

e di

seas

es

WP1

0

Early

dia

gnos

is o

f neu

rode

gene

rativ

e di

seas

e

TTP

WP1

1.1

WP1

1.2

WP1

2

WP1

3

WP1

4

WP1

5.1


Totals

P01

P02

P03

P04a

P04b

P05

P06

P07

P08

P09a

P09b

P10

P11

P12a

P12b

P12d

P13

P14a

P14b

P15a

P15b

P17a

P17b

P20

P21

P22a

P22b

P25

P26

P27

P29b

P31

P32

P33

P34

P35

P36

P37a

P37b

P39

P40a

P40b

P42

P43

P45

P48

P50

P51

P52

P53

P54

P55

P56

Actu

al P

M

Plan

ned

PM

Actu

al P

M43

367

Plan

ned

PM52

457

Actu

al P

M75

1014

1212

69

12

Plan

ned

PM75

1212

1212

69

12

Actu

al P

M98

5310

89

126

Plan

ned

PM50

54

103

1012

6

Actu

al P

M83

1766

Plan

ned

PM67

166

Actu

al P

M22

80,

528

1510

710

2415

710

2120

149

1412

11

Plan

ned

PM23

931

1510

510

224

157

1623

2020

914

99

Actu

al P

M6

6

Plan

ned

PM6

6

Actu

al P

M88

0,5

22

124

3028

Plan

ned

PM99

25

133

3028

Actu

al P

M94

93

64

38

725

114

311

Plan

ned

PM10

410

36

53

88

352

114

36

Actu

al P

M13

15

424

189

2428

172

Plan

ned

PM12

65

424

1812

2428

92

Actu

al P

M18

44

142

3824

226

1212

24

Plan

ned

PM17

44

3538

2413

812

1624

Actu

al P

M18

812

31

1239

2451

3016

Plan

ned

PM20

112

312

3933

5430

18

Actu

al P

M95

212

91

248

30

Plan

ned

PM99

322

324

830

Actu

al P

M74

22

2018

1412

6

Plan

ned

PM72

220

1814

126

Actu

al P

M29

252

11

Plan

ned

PM31

232

41

1

Actu

al P

M1

1

Plan

ned

PM0

Actu

al P

M17

62,

55

3

Plan

ned

PM17

12,

55

53

Actu

al P

M5

0,5

21

1,5

Plan

ned

PM5

32

Actu

al P

M9

0,5

11

11

11

11

Plan

ned

PM7

11

11

11

1

Actu

al P

M43

58

126

47,

5

Plan

ned

PM65

54

1212

67,

512

6

Act

ual P

M14

8812

3692

310

4329

6287

00

4926

00

00

122

6331

24

03

337

3816

512

126

2511

20

1478

3544

214

9331

510

36

012

2440

1427

Plan

ned

PM14

889

4513

334

6329

6287

00

7232

00

00

122

6331

25

43

337

3820

390

126

3511

52

2078

3553

214

9631

510

36

016

2424

1427

WP0

3D

evel

opm

ent o

f rad

ioph

arm

aceu

tical

pro

bes

for n

euro

dege

nera

tion

dise

ases

Par

tner

Per

son

Mo

nth

s p

er W

ork

pac

kag

e (A

C o

wn

sta

ff)

WP0

1U

ltra

high

cer

ebra

l and

hea

rt im

agin

g an

d qu

antit

atio

n w

ith S

ingl

e-Ph

oton

em

itter

s

WP0

2Q

uant

itativ

e m

icro

PET

and

mul

ti-m

odal

ity (P

ET/M

R, O

T/M

R) s

cann

er

deve

lopm

ent

WP0

4.1

Dev

elop

men

t of l

ibra

ry o

f inn

ovat

ive

MR

I pro

bes

and

impr

oved

m

etho

ds fo

r “in

viv

o” c

ellu

lar l

abel

ling

WP0

4.2

Dev

elop

men

t of o

ptic

al a

nd c

ombi

ned

imag

ing

prob

es

WP0

5An

imal

libr

ary

for d

iagn

ostic

mol

ecul

ar im

agin

g in

neu

rosc

ienc

e an

d ca

rdio

vasc

ular

WP0

6Ev

alua

tion

of th

e ro

le o

f est

roge

n re

cept

ors

in a

mou

se m

odel

of

Alzh

eim

er’s

dis

ease

and

gen

erat

ion

of n

ovel

repo

rter s

yste

ms

WP0

7N

on-in

vasi

ve p

heno

typi

ng o

f ani

mal

mod

els

for n

euro

dege

nera

tive

dise

ases

WP0

8.2

Early

dia

gnos

is o

f neu

rode

gene

rativ

e di

seas

e

WP0

9N

euro

infla

mm

atio

n

WP1

0St

em c

ell t

raffi

ckin

g in

the

CN

S

WP1

1.1

Mul

timod

ality

cha

ract

eriz

atio

n of

ath

eros

cler

otic

pla

ques

WP1

1.2

Cha

ract

eriz

atio

n of

myo

card

ial a

ngio

gene

sis

WP1

2C

ardi

ac s

tem

cel

l the

rapy

mon

itore

d by

mol

ecul

ar im

agin

g

WP1

3M

olec

ular

imag

ing

of N

F-ĸB

act

ivat

ion

and

imag

ing

chro

nic

infla

mm

atio

n us

ing

optic

al p

robe

s

WP1

4In

tegr

atin

g ac

tiviti

es

WP1

5.1

Activ

ities

of t

he B

oard

for T

rain

ing

(BO

T)

WP1

5.2

Activ

ities

of t

he B

oard

for D

isse

min

atio

n an

d C

omm

unic

atio

n (B

OD

IC)

WP1

6M

anag

emen

t act

iviti

es

TTP

DiM

I Tra

inin

g Pl

atfo

rms

Tota

l Pro

ject

Per

son

Mon

ths

(AC

ow

n st

aff)



V. Summary explanation of the impact of major deviations from cost budget and from person-month budget

WP1 Ultra high resolution cerebral and heart imaging and quantitation with Single-Photon emitters

Thanks to the prolongation of last DiMI reporting period, P13 and P12b has performed the 3D reconstruction validation on time. All of planned person-months and cost budget dedicated to the evaluation of 3D optical imaging were used for this last DiMI period by Partners P13 and P12b.

WP2 Quantitative microPET and multi-modality (PET/MR, OT/MR) scanner development

There have been no significant deviations from the cost budget. However the person-month budget was at best an estimate for installation and commissioning of a novel instrument to full home office licence conditions and as such has proved to be over optimistic in terms of time scale. However the careful, painstaking, and systematic reconstruction of the instrument should still result in a significant contribution to the establishment of PET/MR imaging for preclinical research. During the final period, JPA5, no DiMI funds have been used to support an individual post doc but have been spent of travel, consumables for pre-clinical studies and in support of reconstructing the PET/MR scanner in the Laboratory for Molecular Imaging.

WP3 Development of radiopharmaceutical probes for neurodegeneration diseases

No major deviation has to be reported.

WP4.1 Development of library of innovative MRI probes and improved methods for “in vivo” cellular labelling

No relevant cost-budget and person-month deviations have to be reported.

WP4.2 Development of optical and combined imaging probes

No major deviations from cost budget have occurred nor from the person-month budget.

WP5 Animal library for diagnostic molecular imaging in neuroscience and cardiovascular

No relevant cost-budget and person-month deviations occurred during this period.

WP6 Evaluation of the role of estrogen receptors in a mouse model of Alzheimer’s disease and generation of novel reporter systems

The major deviation from the original financial plane is attributable to the out-of-budget increased personnel cost.

The studies carried out in the proceeding period led to the generation of a large number of tissues and samples to be analysed, thus in order to complete the study due time we had to add new personnel to perform the experiments necessary.

WP7 Non-invasive phenotyping of animal models for neurodegenerative diseases

There were no major financial deviations encountered

WP8.2 Early diagnosis of neurodegenerative disease

No deviations from cost budget and person-month budget has been encountered.

WP9 Neuroinflammation

No major deviations from cost budget have been reported, there were only insignificant scientific deviations from the plan.

WP10 Stem cell trafficking in the CNS

No deviations from cost budget and person-month budget have been encountered.


WP11.1 Multimodality characterization of atherosclerotic plaques

No major deviations occurred.

WP11.2 Cardiac stem cell therapy monitored by molecular imaging

No relevant cost-budget and person-month deviations occurred.

WP12 Cardiac stem cell therapy monitored by molecular imaging

None

WP13 Molecular imaging of NF-ĸB activation and imaging chronic inflammation using optical probes

Partners 43, 11, 2, 17b, 37b and AP02 have performed the work that was set out, although with minor deviations in terms of successful outputs, and no impact on the person-month budget should be made. Partners 15b and 40b have not made any contributions for the last year’s reporting period.

WP14 Integrating activities

No deviations regarding the cost-budget and person-months occurred.

WP15.1 Activities of the Board for Training (BOT)

No major deviation from cost budget.

WP15.2 Activities of the Board for Dissemination and Communication (BODIC)

No deviations regarding cost-budget and person-months occurred.

WP16 Management of the DiMI network

No major deviations from a financial point of view have incurred.

Section 2 - Form C Financial Statement per Activity for the Contractual Reporting Period 39


Section 2 - Form C Financial Statement per Activity for the Contractual Reporting Period

Please find originals enclosed separately to this report.

Section 3 – Summary Financial Report (Summary Form C)

5 Page 1/1

ContractorThird

party(ies)Contractor

Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested

30.09.2010Type of Instrument Project Title (or Acronym)

Receipts

NoEReporting period number

Eligible costs(in €)

Joint Programme of Activities

(A)

DiMI

Cost model used

Organisation Short Name

Of which Management of Consortium ActivitiesContractor

n°

Type of activities

To (dd/mm/yyyy)

Total eligible costs (A)

From (dd/mm/yyyy) 01.04.2009

Summary Financial Report

LSHB-CT-2005-512146Contract N°

EC contribution

Direct eligible costs 390.237,95 0,00 123.126,57 0,00 390.237,95 0,00

of which direct eligible costs of subcontracting

1.620,00 0,00 1.620,00 0,00 1.620,00 0,00

Indirect eligible costs 77.723,59 0,00 24.301,31 0,00 77.723,59 0,00

Adjustment on previous period(s)

-9,46 0,00 0,00 0,00 -9,46 0,00

Total eligible costs 467.952,08 0,00 147.427,88 0,00 467.952,08 0,00

Direct eligible costs 45.361,05 0,00 576,30 0,00 45.361,05 0,00


576,30 0,00 576,30 0,00 576,30 0,00

Indirect eligible costs 8.956,95 0,00 0,00 0,00 8.956,95 0,00


0,00 0,00 0,00 0,00 0,00 0,00

Total eligible costs 54.318,00 0,00 576,30 0,00 54.318,00 0,00



1.589,00 0,00 1.589,00 0,00 1.589,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.000,00 0,00 0,00 0,00 1.000,00 0,00



-328,23 0,00 0,00 0,00 -328,23 0,00




2.530,30 0,00 2.530,30 0,00 2.530,30 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




530,00 0,00 530,00 0,00 530,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00


77.932,74

8University of

AntwerpAC 0,00 0,00 58.676,00 58.676,00

7

Rigshospitalet,

Neurobiology Research

Unit, Copenhagen

AC 0,00 0,00 77.932,74

74.198,94

6University of

MilanAC 0,00 0,00 113.665,34 113.665,34

5

lnstitut d'lnvestigaci

ons Biomèdiques August Pi i

Sunyer'

AC 0,00 0,00 74.198,94

29.760,75

4

Université de Tours

François Rabelais

AC 0,00 0,00 130.297,54 130.297,54

3

Università degli Studi di

Torino - Dipartimento

di Chimica I.F.M.

AC 0,00 0,00 29.760,75

467.952,08

2

The Chancellor, Masters and Scholars of

the University of Cambridge

AC 0,00 0,00 54.318,00 54.318,00

1

Universität zu Köln-

Universitätsklinikum Köln

AC 0,00 0,00 467.952,08

Section 3 – Summary Financial Report (Summary Form C) 41


5 Page 1/1

ContractorThird


Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested


Receipts




(A)

DiMI

Cost model used



n°

Type of activities

To (dd/mm/yyyy)





EC contribution



0,00 0,00 0,00 0,00 0,00 0,00



-5.444,48 0,00 0,00 0,00 -5.444,48 0,00




2.000,00 0,00 2.000,00 0,00 2.000,00 0,00



279,72 0,00 0,00 0,00 279,72 0,00




600,00 0,00 0,00 0,00 600,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 1.360,90 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.200,00 0,00 1.200,00 0,00 1.200,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




200,00 0,00 200,00 0,00 200,00 0,00



7.462,88 0,00 0,00 0,00 7.462,88 0,00




1.281,80 0,00 1.281,80 0,00 1.281,80 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.169,89 0,00 1.169,89 0,00 1.169,89 0,00



-64,27 0,00 0,00 0,00 -64,27 0,00


78.395,31

10Technischen Universität München

AC 0,00 0,00 88.630,68 88.630,68

9

Centre National de la

Recherche Scientifique

FCF 0,00 0,00 156.790,62

FCF

11University of

Oslo

13BIOSPACE

LAB

86.750,53

12Commissariat à l'Energie Atomique'

FC 0,00 0,00 196.369,49 158.698,20

0,00 86.750,53AC 0,00

0,00 80.829,20 57.826,64

14Katholieke Universiteit

LeuvenAC 0,00 0,00 111.982,90 111.982,90

0,00

30.508,87

17

Imperial College of Science

technology and Medicine

AC 0,00 0,00 37.159,46 37.159,46

15Lund

University0,00 30.508,87AC 0,00

5 Page 1/1

ContractorThird


Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested


Receipts




(A)

DiMI

Cost model used



n°

Type of activities

To (dd/mm/yyyy)





EC contribution



1.100,00 0,00 1.100,00 0,00 1.100,00 0,00

Indirect eligible costs 393,51 0,00 0,00 0,00 393,51 0,00


0,00 0,00 0,00 0,00 0,00 0,00




656,98 0,00 656,98 0,00 656,98 0,00



0,00 0,00 0,00 0,00 0,00 0,00




848,50 0,00 848,50 0,00 848,50 0,00



-241,09 0,00 0,00 0,00 -241,09 0,00




800,00 0,00 800,00 0,00 800,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00


Direct eligible costs 0,00 0,00 0,00 0,00 0,00 0,00


0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00

Total eligible costs 0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.220,00 0,00 1.220,00 0,00 1.220,00 0,00



-529,43 0,00 0,00 0,00 -529,43 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00


24Forschungsz

entrum Jülich GmbH

FC

18

Institut de Recerca de

l'Hospital de la Santa Creu

i Sant Pau

AC 0,00 3.461,08 3.461,08

20UNIVERSITY

OF EDINBURGH

AC 0,00 0,00 13.616,60 13.616,60

0,00

59.498,75

22

Karolinska lnstitutet,

Department of Clinical

Neuroscience, Psychiatry

Section

AC 0,00 0,00 45.889,78 45.889,78

21

Universitätsklinikum Bonn

für den Fachbereich

Medizin

0,00 59.498,75AC 0,00

0,00 0,00 0,00

25

Max-Planck-Institute for Neurological

Research, Cologne

AC 0,00 0,00 25.074,51 25.074,51

0,00

17.472,10

27

Center for Bio-lmaging, Sahlgrenska Akademin, Göteborg

Universitet

AC 0,00 0,00 0,00 0,00

26

Cardio-Vascular Research lnstitute

Maastricht

0,00 17.472,10AC 0,00



5 Page 1/1

ContractorThird


Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested


Receipts




(A)

DiMI

Cost model used



n°

Type of activities

To (dd/mm/yyyy)





EC contribution



0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




658,52 0,00 658,52 0,00 658,52 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.800,00 0,00 1.800,00 0,00 1.800,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.383,13 0,00 1.383,13 0,00 1.383,13 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.560,00 0,00 1.560,00 0,00 1.560,00 0,00



387,26 0,00 0,00 0,00 387,26 0,00




0,00 0,00 0,00 0,00 0,00 0,00



-495,98 0,00 0,00 0,00 -495,98 0,00


29 0,00 0,00 0,00 0,00

31University of

Newcastle upon Tyne

AC 0,00 0,00 67.113,08 67.113,08

University Hospital

GroningenAC

10.237,54

33

CONSIGLIO NAZIONALE

DELLE RICERCHE

FC 0,00 0,00 73.162,13 9.900,00

32Technische Universiteit Eindhoven

AC 0,00

0,00 10.237,54AC 0,00

0,00 11.977,38 11.977,38

35Durham

UniversityAC 0,00 0,00 37.439,14 37.439,14

34Fondazione

Telethon

18.438,72

37

Leiden University

Medical Center

AC 0,00 0,00 47.177,82 47.177,82

36Università Vita-Salute

San Raffaele0,00 18.438,72AC 0,00

5 Page 1/1

ContractorThird


Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested


Receipts




(A)

DiMI

Cost model used



n°

Type of activities

To (dd/mm/yyyy)





EC contribution



547,04 0,00 450,00 0,00 547,04 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



-100,84 0,00 0,00 0,00 -100,84 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.488,00 0,00 0,00 0,00 1.488,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




0,00 0,00 0,00 0,00 0,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00


AC 0,00 0,00 23.074,64 23.074,64

40

Westfälische Wilhelms-Universität

Münster

AC 0,00 0,00 55.125,42 55.125,42

39Université de

Liege

8.350,00

43 Cgene FCF 0,00 0,00 54.030,00 54.030,00

42

CYCERON / Cerebral lmaging

Centre for Research on Neuroscienc

e

AC 0,00

0,00 8.350,00AC 0,00

0,00 3.463,98 3.463,98

47

LABORATOIRES

CYCLOPHARMA

FC 0,00 0,00 0,00 0,00

45Universidad de Navarra

0,00

50

Univerzita Karlova - Charles

University, Faculty of Science

AC 0,00 0,00 12.931,20 12.931,20

48

medres - medical research

GmbH

0,00 0,00FC 0,00



5 Page 1/1

ContractorThird


Third party(ies)

ContractorThird


Third party(ies)

Maximum Requested


Receipts




(A)

DiMI

Cost model used



n°

Type of activities

To (dd/mm/yyyy)





EC contribution



885,00 0,00 885,65 0,00 885,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




500,00 0,00 500,00 0,00 500,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




2.600,00 0,00 2.600,00 0,00 2.600,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00




1.115,72 0,00 0,00 0,00 1.115,72 0,00



-247,49 0,00 0,00 0,00 -247,49 0,00




0,00 0,00 0,00 0,00 0,00 0,00



-2.337,25 0,00 0,00 0,00 -2.337,25 0,00




500,00 0,00 500,00 0,00 500,00 0,00



0,00 0,00 0,00 0,00 0,00 0,00


2.531.905,63 0,00 177.853,85 0,00 2.531.905,63 0,00 0,00 0,00

2.531.905,62 0,00 177.853,85 0,00

0,00

Maximum calculated EC contribution for the reporting period (in €) without taking into account receipts 2.531.905,62 177.853,85

2.531.905,62

Amount of the financial interests generated by the prefinancing

0,00Total eligible costs

2.531.905,63 177.853,85 2.531.905,63

Requested EC contribution for the reporting period (in €) 2.329.574,33

2.531.905,62 2.329.574,33

FC 0,00 0,00 42.000,00 42.000,00

52

Institute of Experimental

Medicine, Academy of Sciences of the Czech Republic

AC 0,00 0,00 13.014,96 13.014,96

51

Institute of Atomic Energy,

Radioisotope Centre

POLATOM

13.948,18

54University of Manchester

AC 0,00 0,00 59.791,73 59.791,73

53Universität

Regensburg

AC 0,00

0,00 13.948,18AC 0,00

0,00 18.313,76 18.313,76

56University of

Duisburg-Essen

AC 0,00 0,00 1.480,00 1.480,00

55VU University

Medical Centre

PERIODIC REPORT ON THE DISTRIBUTION OF THE COMMUNITY'S

CONTRIBUTION

DIMI

DIAGNOSTIC MOLECULAR IMAGING

A NETWORK OF EXCELLENCE FOR IDENTIFICATION

OF NEW IMAGING MARKERS

FOR DIAGNOSTIC PURPOSE

PROJECT NO.: LSHB-CT-2005-512146

START DATE OF PROJECT: APRIL 1ST 2005

DURATION: 66 MONTHS

PROJECT COORDINATOR NAME: PROF. DR. ANDREAS JACOBS

PROJECT COORDINATOR ORGANISATION NAME: KUK

PERIOD COVERED IN THIS REPORT: APRIL 1ST 2009 TO SEPTEMBER 30TH 2010

DATE OF PREPARATION: NOVEMBER 15TH 2010

SIXTH FRAMEWORK PROGRAMME

Periodic Report on the Distribution of the Community’s Contribution 49

DiMI Annual Report 2010 Periodic Report on the Distribution of the Community's Contribution

As described in JPA5 among all the 59 DiMI partners, 4 levels of participation have been

differentiated:

Level 1:

Level 1 partner are work package (WP) and technology and training platform (TTP) leaders and

will conduct the JPA over the full 5 years. Partner Level 1 received the country equivalent of the

salary for one post-doc and supplies to run the TTP and to guide the research related to one WP.

Level 1 partners are: KUK (1) together with UNIMAN (54), UCAM-WBIC (2), UniTo (3), UniTours I

(4a), IDIBAPS (5), UNIMI (6), RH-NRU (7), UA (8), CNRS_Bordeaux (9a), NUK_TUM (10), UiO

(11), CEA_Lige (12a), BIOSPACE (13).

Level 2:

Level 2 partners are very active partners in the consortium as well and two of them also lead a

work package but not a technology and training platform. Partner leading a work package will

receive the equivalent of half a post-doc and supplies. This year this amounted to 33.000 €. Those

partner contributing more than 4,5% to the overall JPA5 budget received 29.000 € and those

contributing between 3-4,5% received 25.000 €. The Level 2 partners were: KULeuven R&D I

(14a), KULeuven II (14b), Tu/e (32), DUR (35), UKM I (40a).

Level 3:

Level 3 partners are active in the consortium and contributed a lot to the JPA5. They received

between 9.000 € and 17.000 € according to their contribution. Partners who contribute 2-3 % to the

total costs of JPA5 received 26.000 €, partners who contribute 1-2 % received 13.000 € and

partners who contribute 0,5-1 % received 9.000 €. The Level 3 partners involved in the JPA5 and

contributing between 0,5-3 % to the total costs were: CEA_ImaGene (12b), ULUND (15a), UKB

(21), KI I (22a), KI II (22b), MPInF (P25), CBI (27), UNEW (31), CNR-IBB (33), FTELE (34), UVita-

P (36), LUMC I (37a), LUMC II (37b), UKM II (40b), CYCERON (42), Charles University (50), IEM

ASCR (52), KUR (53), UE (56).

Level 4:

Level 4 partners (18) contributed not or only very limited to JPA5. Level 4 partners who contribute

less than 0,5% to the total costs of JPA3 received 5.000 € for travelling, participating in training

and dissemination activities and additional costs for their contribution. The Level 4 partners

involved in the JPA5 and contributing less than 0.5% are: UniTours II (4b), CNRS_Paris (9b),

CNRS_INP (9c), CEA_Grenoble (12c), CEA_INSTN (12d), ULUND II(15b), Imperial College I

(17a), Imperial College (17b), Hospital Sant Pau (18), UEDIN (20), FZJ (24), CARIM (26), AZG II

(29b), ULG (39), CGene (43), UNAV (45), Cyclopharma (47), MEDRES (48), Polatom (51) Vumc

(55).

FLEXIFUND:

According to the decision of the steering committee the following partners received additional

flexifunds: UCAM-WBIC (2), UniTours I (4a), IDIBAPS (5), RH-NRU (7), KULeuven R&D I (14a),

Tu/e (32), CNR-IBB (33), CYCERON (42), CGene (43).

50 Periodic Report on the Distribution of the Community’s Contribution

Periodic Report on the Distribution of the Community’s Contribution DiMI Annual Report 2010

From To From To From To From To From To01.04.05 31.03.06 01.04.06 31.03.07 01.04.07 31.03.08 01.04.08 31.03.09 01.04.09 30.09.10

DateAmount

(A)Date

Amount(B)

DateAmount

(C)Date

Amount(D)

DateAmount

(E)

20.07.05 2.802.000,00 01.12.06 1.565.800,00 20.09.07 2.531.800,00 17.10.08 2.174.479,20 30.09.09 1.000.300,32 10.074.379,52

Contractor n°


Country Code

Date(s) (5)Amount(s)

(A') (5)Date(s) (5)

Amount(s)(B') (5)


(C') (5)Date(s) (5)

Amount(s)(D') (5)


(E') (5)

27.07.05 480.135,28 06.09.06 74.201,00 20.09.07 487.876,72 22.10.08 393.479,20 01.10.09 467.952,08 1.903.644,2822.12.06 164.850,95 164.850,95

0,000,00

Total 480.135,28 Total 239.051,95 Total 487.876,72 Total 393.479,20 Total 467.952,08 2.068.495,23

27.07.05 79.030,00 08.09.06 11.290,00 24.09.07 81.600,00 22.10.08 69.000,00 01.10.09 32.200,00 273.120,0028.12.06 56.542,22 01.10.09 18.000,00 74.542,22

0,000,00

Total 79.030,00 Total 67.832,22 Total 81.600,00 Total 69.000,00 Total 50.200,00 347.662,22

27.07.05 79.030,00 08.09.06 11.290,00 24.09.07 81.600,00 22.10.08 74.000,00 01.10.09 35.000,00 280.920,0028.12.06 62.824,69 62.824,69

0,000,00


27.07.05 101.080,00 08.09.06 14.440,00 24.09.07 107.400,00 04.11.08 86.000,00 01.10.09 23.261,16 332.181,1628.12.06 59.950,38 08.10.09 4.000,00 63.950,38

0,000,00


27.07.05 83.930,00 08.09.06 11.990,00 24.09.07 84.000,00 22.10.08 82.000,00 01.10.09 35.000,00 296.920,0028.12.06 66.497,34 01.10.09 5.000,00 71.497,34

0,000,00


27.07.05 86.030,00 08.09.06 12.290,00 24.09.07 84.000,00 22.10.08 74.000,00 18.11.09 35.000,00 291.320,0028.12.06 68.344,80 68.344,80

0,000,00


27.07.05 91.490,00 08.09.06 13.070,00 24.09.07 92.400,00 22.10.08 86.000,00 01.10.09 37.800,00 320.760,0028.12.06 72.729,73 08.10.09 8.000,00 80.729,73

0,000,00


27.07.05 97.020,00 08.09.06 13.860,00 24.09.07 96.000,00 22.10.08 92.000,00 01.10.09 42.700,00 341.580,0028.12.06 77.125,79 77.125,79

0,000,00


27.07.05 98.244,72 12.09.06 14.139,00 24.09.07 89.484,80 22.10.08 85.000,00 01.10.09 5.700,00 292.568,5213.02.07 35.838,72 19.01.09 20.000,00 55.838,72

0,000,00


27.07.05 98.980,00 06.09.06 14.140,00 24.09.07 49.200,00 22.10.08 85.000,00 02.10.09 37.800,00 285.120,0022.12.06 54.012,91 24.01.08 49.200,00 103.212,91

0,000,00


Project Title (or Acronym) DiMI

8 UA

9 CNRS

Reporting Period 4Total Amount

(I') (6)

2 UCAM-WBC

Reporting Period 5Reporting Period 1 Reporting Period 2 Reporting Period 3

Community's prefinancing (or payment) sent to the coordinator (1)

Distribution of the Community's prefinancing (or payment) between contractors according to the consortium decision(s) (4)

Total Amount(I) (3)

Reporting Period 2 (2) Reporting Period 3 (2) Reporting Period 4 (2) Reporting Period 5 (2)Reporting Period 1 (2)

7 RH-NRU

6

3 UniTo

4 UnivTours

UNIMI

5 IDIBABS

Part I

Part II

1

KUK (incl. FZJ + CBI (till 03/07) + Cyclopharma +

Visgenyx (resolved 2008) + flex fund + shared

expenses)

Total (X)

Report on the Distribution of the Community's contribution

512146Type of Instrument NoE

10 NUK-TUM

1



Contractor n°


Country Code


(A') (5)Date(s) (5)

Amount(s)(B') (5)


(C') (5)Date(s) (5)

Amount(s)(D') (5)


(E') (5)

27.07.05 104.440,00 08.09.06 14.920,00 24.09.07 105.600,00 22.10.08 103.000,00 01.10.09 47.600,00 375.560,0028.12.06 88.024,30 88.024,30

0,000,00


27.07.05 137.410,00 08.09.06 19.630,00 25.09.07 142.450,00 22.10.08 116.000,00 01.10.09 51.100,00 466.590,0023.03.06 40.000,00 28.12.06 95.488,71 135.488,71

0,000,00


27.07.05 166.250,00 08.09.06 23.750,00 25.09.07 114.000,00 22.10.08 61.000,00 01.10.09 23.100,00 388.100,0028.12.06 76.599,57 76.599,57

0,000,00


27.07.05 89.250,00 08.09.06 12.750,00 25.09.07 115.200,00 22.10.08 82.000,00 01.10.09 23.200,00 322.400,0028.12.06 83.469,46 01.10.09 12.000,00 95.469,46

0,000,00


27.07.05 29.400,00 08.09.06 4.200,00 25.09.07 36.000,00 22.10.08 28.000,00 01.10.09 4.000,00 101.600,0028.12.06 19.865,74 18.11.09 10.400,00 30.265,74

0,000,00


27.07.05 28.140,00 08.09.06 4.020,00 25.09.07 9.000,00 22.10.08 28.000,00 07.12.09 4.000,00 73.160,0028.12.06 6.677,56 6.677,56

0,000,00


27.07.05 8.400,00 08.09.06 1.200,00 25.09.07 9.000,00 0,00 18.600,0028.12.06 6.338,78 6.338,78

0,000,00

Total 8.400,00 Total 7.538,78 Total 9.000,00 Total 0,00 Total 0,00 24.938,78

27.07.05 8.400,00 08.09.06 1.200,00 25.09.07 9.000,00 22.10.08 8.000,00 26.600,0028.12.06 6.459,87 6.459,87

0,000,00

Total 8.400,00 Total 7.659,87 Total 9.000,00 Total 8.000,00 Total 0,00 33.059,87

27.07.05 29.820,00 06.09.06 4.260,00 25.09.07 13.500,00 22.10.08 20.000,00 67.580,0022.12.06 12.806,82 12.806,82

0,000,00

Total 29.820,00 Total 17.066,82 Total 13.500,00 Total 20.000,00 Total 0,00 80.386,82

27.07.05 27.300,00 08.09.06 3.900,00 25.09.07 44.000,00 22.10.08 28.000,00 01.10.09 20.800,00 124.000,0028.12.06 38.256,84 13.11.07 5.000,00 43.256,84

0,000,00


Reporting Period 1 Reporting Period 2 Reporting Period 3 Reporting Period 4

14 KULURD

Total Amount(I') (6)

11 UIO

Reporting Period 5

DiMI

15 ULUND

12 CEA

13 BIOSPACE

512146

Part II Distribution of the Community's prefinancing (or payment) between contractors according to the consortium decision(s) (4)

Type of Instrument NoE Project Title (or Acronym)


20 UEDIN

17 ICL

18 HSP

22 KI

21 UKB

2



Contractor n°


Country Code


(A') (5)Date(s) (5)

Amount(s)(B') (5)


(C') (5)Date(s) (5)

Amount(s)(D') (5)


(E') (5)

0,00 0,00 0,00 0,00 0,000,00 0,00

0,000,00

Total 0,00 Total 0,00 Total 0,00 Total 0,00 Total 0,00 0,00

27.07.05 36.750,00 06.09.06 5.250,00 17.10.07 83.330,00 22.10.08 38.000,00 02.10.09 13.600,00 176.930,0022.12.06 20.450,02 20.450,02

0,000,00


27.07.05 36.750,00 08.09.06 5.250,00 25.09.07 9.000,00 22.10.08 14.000,00 18.11.09 4.000,00 69.000,0028.12.06 17.806,82 17.806,82

0,000,00


0,00 0,00 04.12.07 17.358,48 22.10.08 14.000,00 01.10.09 7.200,00 38.558,480,00 0,00

0,000,00

Total 0,00 Total 0,00 Total 17.358,48 Total 14.000,00 Total 7.200,00 38.558,48

27.07.05 8.400,00 08.09.06 1.200,00 25.09.07 17.000,00 22.10.08 8.000,00 01.10.09 4.000,00 38.600,0028.12.06 13.188,18 13.188,18

0,000,00


27.07.05 49.700,00 08.09.06 7.100,00 26.09.07 22.800,00 22.10.08 20.000,00 18.11.09 10.400,00 110.000,0028.12.06 39.508,88 39.508,88

0,000,00


27.07.05 36.750,00 08.09.06 5.250,00 25.09.07 57.600,00 22.10.08 44.000,00 01.10.09 23.200,00 166.800,0028.12.06 26.301,05 01.10.09 6.000,00 32.301,05

0,000,00


27.07.05 17.150,00 13.09.06 2.450,00 26.09.07 17.000,00 22.10.08 8.000,00 01.10.09 7.200,00 51.800,0028.12.06 6.677,36 08.10.09 990,00 7.667,3613.02.07 2.225,85 2.225,85

0,00Total 17.150,00 Total 11.353,21 Total 17.000,00 Total 8.000,00 Total 8.190,00 61.693,21

27.07.05 24.150,00 13.09.06 3.450,00 26.09.07 9.000,00 22.10.08 14.000,00 01.10.09 10.400,00 61.000,0028.12.06 14.806,82 14.806,82

0,000,00


27.07.05 49.700,00 13.09.06 7.100,00 25.09.07 45.600,00 22.10.08 50.000,00 01.10.09 26.400,00 178.800,0028.12.06 39.508,88 39.508,88

0,000,00


35 DUR


Type of Instrument NoE Project Title (or Acronym) DiMI 512146


Reporting Period 1 Reporting Period 2 Reporting Period 3 Reporting Period 4 Reporting Period 5Total Amount

(I') (6)

27 CBI (since 04/07)

held at P1 KUK until period 2

34 FTELE

29

CNR-IBB

UniGro

26 CARIM

24 FZJheld at P1 KUK

25 MPIFNF

31 UNEW

32 TU/e

33



Contractor n°


Country Code


(A') (5)Date(s) (5)

Amount(s)(B') (5)


(C') (5)Date(s) (5)

Amount(s)(D') (5)


(E') (5)

27.07.05 25.200,00 13.09.06 3.600,00 26.09.07 27.000,00 22.10.08 26.000,00 01.10.09 13.600,00 95.400,0028.12.06 26.432,00 26.432,00

0,000,00


27.07.05 22.400,00 13.09.06 3.200,00 25.09.07 44.000,00 22.10.08 40.000,00 01.10.09 24.000,00 133.600,0013.02.07 37.822,92 37.822,92

0,000,00


27.07.05 8.400,00 13.09.06 1.200,00 26.09.07 9.000,00 22.10.08 8.000,00 18.11.09 4.000,00 30.600,0028.12.06 5.564,63 5.564,63

0,000,00


27.07.05 69.090,00 06.09.06 9.870,00 24.09.07 72.600,00 22.10.08 70.000,00 02.10.09 26.400,00 247.960,0022.12.06 43.938,33 43.938,33

0,000,00


27.07.05 36.750,00 13.09.06 5.250,00 26.09.07 27.000,00 22.10.08 26.000,00 01.10.09 13.600,00 108.600,0028.12.06 26.432,00 01.10.09 5.000,00 31.432,00

0,000,00


27.07.05 8.400,00 13.09.06 1.200,00 26.09.07 9.000,00 22.10.08 14.000,00 01.10.09 4.000,00 36.600,0028.12.06 10.188,18 01.10.09 12.000,00 22.188,18

0,000,00


27.07.05 8.400,00 14.09.06 1.200,00 26.09.07 9.000,00 22.10.08 8.000,00 01.10.09 4.000,00 30.600,0028.12.06 11.129,26 11.129,26

0,000,00


0,00 0,00 0,00 0,00 0,000,00 0,00

0,000,00

Total 0,00 Total 0,00 Total 0,00 Total 0,00 Total 0,00 0,00

27.07.05 8.400,00 15.09.06 1.200,00 27.09.07 9.000,00 0,00 18.600,0022.12.06 6.677,56 6.677,56

0,000,00

Total 8.400,00 Total 7.877,56 Total 9.000,00 Total 0,00 Total 0,00 25.277,56

4

48 MEDRES

45 UNAV

47 Cyclopharmaheld at P1 KUK

42 CYCERON

43 CGENE

39 ULG

40 UKM

Reporting Period 1 Reporting Period 2

36 Uvita-P

37 LUMC

Reporting Period 3 Reporting Period 4

512146

Total Amount(I') (6)

Reporting Period 5

Project Title (or Acronym) DiMI



Type of Instrument NoE



Contractor n°


Country Code


(A') (5)Date(s) (5)

Amount(s)(B') (5)


(C') (5)Date(s) (5)

Amount(s)(D') (5)


(E') (5)

27.07.05 16.590,00 14.09.06 2.370,00 26.09.07 9.000,00 22.10.08 20.000,00 01.10.09 10.400,00 58.360,0028.12.06 14.129,26 14.129,26

0,000,00


27.07.05 8.400,00 14.09.06 1.200,00 26.09.07 9.000,00 22.10.08 8.000,00 01.10.09 4.000,00 30.600,0028.12.06 6.677,56 6.677,56

0,000,00


27.07.05 16.590,00 14.09.06 2.370,00 26.09.07 37.000,00 22.10.08 20.000,00 01.10.09 7.200,00 83.160,0028.12.06 11.129,26 11.129,26

0,000,00


0,00 0,00 24.09.07 27.000,00 22.10.08 20.000,00 02.10.09 10.400,00 57.400,0022.12.06 10.000,00 10.000,00

0,000,00

Total 0,00 Total 10.000,00 Total 27.000,00 Total 20.000,00 Total 10.400,00 67.400,00

0,00 0,00 26.09.07 15.000,00 22.10.08 50.000,00 23.11.09 24.000,00 89.000,0027.02.07 5.000,00 5.000,00

0,000,00


0,00 0,00 26.09.07 17.000,00 22.10.08 14.000,00 24.11.09 4.000,00 35.000,0013.02.07 7.500,00 7.500,00

0,000,00


0,00 0,00 25.09.07 27.000,00 22.10.08 20.000,00 02.10.09 10.400,00 57.400,0022.12.06 10.000,00 10.000,00

0,000,00


Total 2.451.750,00 Total 1.916.050,00 Total 2.531.800,00 Total 2.174.479,20 Total 1.274.003,24 10.348.082,44

Total Amount

-273.702,92

Jacobs

0,00

Part IIIDifference between Community's prefinancing (or payment) sent to the coordinator and Total Distribution of the Community's prefinancing (or payment) between contractors according

to the consortium decision(s) (4)

Name (8) Surname (8)Date

(dd/mm/yyyy)

Total (Y)

5

Andreas H.

56 UE

54 UNIMAN

50

51 POLATOM

55 Vumc

52 IEM ASCR

53 KUR

Charles University


Reporting Period 1 Reporting Period 2 Reporting Period 3 Reporting Period 4 Reporting Period 5Total Amount

(I') (6)


Type of Instrument NoE Project Title (or Acronym) DiMI 512146

Reporting Period 3 Reporting Period 4 Reporting Period 5Reporting Period 1 Reporting Period 2

I certify that the information set out in this(these) form(s) is accurate and correct and agreed by all contractors.

0,00 -1274003,24 Community's prefinancing (or payment) not yet distributed between contractors (Z) (7)

350250,00 -350250,00

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