xSPECT – Advances in Nuclear Medicine · Department of Nuclear Medicine. LMU Munich Mandatory...
Transcript of xSPECT – Advances in Nuclear Medicine · Department of Nuclear Medicine. LMU Munich Mandatory...
Department of Nuclear MedicineUniversity Hospital of Munich
chairman: Prof. Dr. med. P. Bartenstein
xSPECT – Advances in Nuclear Medicine27. Ulusal Nükleer Tıp Kongresi
01. – 05. Nisan 2015, Adana, Turkey
Harun IlhanDepartment of Nuclear MedicineUniversity Hospital of MunichMarchioninistr. 15, 81377 Munich, GermanyEmail: [email protected]
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Nuclear Medicine and Theranostic
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
What is „theranostics“?
Department of Nuclear MedicineLMU Munich
Combination of therapy and diagnostic
Therapeutic procedure or product followed by diagnostic procedure(e.g. drug efficacy for patients with specific diseases)
Diagnostic procedure followed by therapeutic procedure(e.g. imaging procedure for therapy indication)
Tumor characterization by specific radiopharmaceuticals
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Personalized medicine
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Theranostics example
Department of Nuclear MedicineLMU Munich
Diagnostic Ga-68 DOTA TATE PET for patient evaluation for Peptide-Receptor-Radionuclide-Therapy with Lu-177 DOTA TATE
68Ga-DOTATATE
177Lu
HOH2C
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COOHHOOC
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90Y68Ga
HOH2C
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90Y
68Ga-DOTATATE
90Y-DOTATATE177Lu-DOTATATE
177LuHOH2C
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177Lu
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
2005
4509 FDG803 Ga-TATE583 FET282 FEC
84 Alzheimercomp. 69 FDOPA50 DMFP/FP
8 Ga-PSMA .6389 total
PET Radiopharmaceuticals 2005 and 2013
2490 FDG122 FET
54 Choline2666 total
2005
2013
FDG93,40%
FET4,58%
Cholin2,03%
FDG70,57%
FET9,13%
Ga-TATE12,57%
FEC4,43%
FDOPA1,08%
DMFP0,67%
FP0,11%
Ga-PSMA0,13%
F-18 AlzComp1,31%
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Do we need scintigraphy in this situation?
Department of Nuclear MedicineLMU Munich
Increasing demand for SPECT
Number of scintigraphic investigations at theDepartment of Nuclear Medicine, LMU Munich 2006 - 2013
years
Num
bero
fInv
estig
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ns
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of Molecular Imaging and SPECT
Department of Nuclear MedicineLMU Munich
EANM 2007 Statistics Survery: Σ 7.5 x 106 per year
Installed cameras:PET and PET/CT: 503SPECT Cameras: 4250
0,0E+00
5,0E+05
1,0E+06
1,5E+06
2,0E+06
2,5E+06
Ske
leta
l
Endo
crin
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Myo
card
Oth
ers
Lun
g
PET
+P
ET/C
T
Ren
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In-Vivo Diagnostic Procedures in the USA
Delbeke and Segall; J Nucl Med 2011Status of and trends in Nuclear Medicine in the United States:
Total: 17 x 106 per yearPET/CT and PET: 1.5 x 106 per year
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of SPECT
Department of Nuclear MedicineLMU Munich
www.eanm.org – Technopolis report summary
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of SPECT
Department of Nuclear MedicineLMU Munich
www.eanm.org – Technopolis report summary
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of SPECT
Department of Nuclear MedicineLMU Munich
www.eanm.org – Technopolis report summary
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Advantages of SPECT imaging
Department of Nuclear MedicineLMU Munich
Installed camera basis
Logistics(Availability of kits, radiopharmaceutical production and distribution)
Development of new camera types / reconstruction algorithms
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
PET vs. SPECT in clinical oncology
Department of Nuclear MedicineLMU Munich
Mandatory requirements for the future:
adequate radiopharmaceuticals
development in camera systems and reconstruction methods
Inferiority of SPECT in terms of spatial resolution and quantification
However, due to availability, costs, logistics SPECT might be the better choice
Siemens Symbia Intevo
the world`s first xSPECT system
„see the unseen“
„quantify the difference“
„adapt the lowest dose“
„double the throughput“
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
PET vs. SPECT in clinical oncology
Department of Nuclear MedicineLMU Munich
Mandatory requirements for the future:
adequate radiopharmaceuticals
development in camera systems and reconstruction methods
Inferiority of SPECT in terms of spatial resolution and quantification
However, due to availability, costs, logistics SPECT might be the better choice
Siemens Symbia Intevo
the world`s first xSPECT system
„see the unseen“
„quantify the difference“
„adapt the lowest dose“
„double the throughput“
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Radiopharmaceuticals for theranostic approaches
Department of Nuclear MedicineLMU Munich
I-131
I-131 MIBG
Ga-68 / Lu-177 somatostatine receptor ligands
Ga-68 / Lu-177 PSMA
Y-90 Ibritumomab
Y-90 Microspheres
Ra-223 Dicholride
Sm-153 EDTMP
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Radiopharmaceuticals for theranostic approaches
Department of Nuclear MedicineLMU Munich
I-131
I-131 MIBG
Ga-68 / Lu-177 somatostatine receptor ligands
Ga-68 / Lu-177 PSMA
Y-90 Ibritumomab
Y-90 Microspheres
Ra-223 Dicholride
Sm-153 EDTMP
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Department of Nuclear MedicineLMU Munich
Somatostatine-receptor ligands for therapy and diagnostics
HOH2C
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OH
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NH2
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COOHHOOC
HOOC
90Y
68Ga-DOTATATE
90Y-DOTATATE177Lu-DOTATATE
HOH2C
OH
HN
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OH
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COOHHOOC
HOOC
90Y
177Lu
68Ga
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Neuroendocrine Tumors
Department of Nuclear MedicineLMU Munich
DOTATATE-PET Conventional Octreotide-scintigraphy
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of quantification and dosimetry
Department of Nuclear MedicineLMU Munich
Courtesy Juri Ruf; Dept. of Nuclear Medicine, Univ. Freiburg
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Neuroendocrine Tumors
Department of Nuclear MedicineLMU Munich
60yr patient, NET of the pancreas with lymphnode and hepatic filiaeGa-68 DOTATATE PET/CT prior to therapy and after 2 cycles
2 x therapywith 7400 MBq
177Lu-DOTATATE
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
RESULTS – 177LU-DOTATATE
310 patients1
CR 2%, PR 28%, MR 16%
SD 35%
PD 20%
Median TTP 40 months
Median survival
46 months
Significant improvement of QoLin 50 patients2
1 Kwekkeboom et al., JCO 20082 Teunissen et al., JCO 2004
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
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ther
apie
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DOTA-TATE therapies / year
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
PRRT THERAPY AND THERAPY MONİTORİNG
177Lu-DOTATATEPRRT
Planar dynamicscintigraphy
Therapy
Planar + SPECT
Blood samplesUrine
72h p.i.
Planar + SPECT
Blood samples
Planar + SPECT
Blood samples
Planar + SPECT
Blood samples
24h p.i. 48h p.i.1h p.i.Diagnostic
PET/CT
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Neuroendocrine Tumors
Department of Nuclear MedicineLMU Munich
38yr female patient, NET of the ileum with liver and spleen metastases
Currently undergoing 3rd cycle of Lu-177-DOTATATE treatment
Day 0 Day 1 Day 2 Day 3
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-DOTATATE SPECT/CT: xSPECT Reconstruction
Department of Nuclear MedicineLMU Munich
upper energy window (both available)currently no quantitation available (at our site)
Day 0 Day 1 Day 2 Day 3Day 0 Day 1
Day 2 Day 3
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-DOTATATE SPECT/CT: LMU-Reconstruction
Department of Nuclear MedicineLMU Munich
DOSE ESTIMATIONS„manual“ method
Day 0 Day 1 Day 2 Day 3Day 0
SPECT/CT (day 0)
SPECT/CT (day 3)
SPECT/CT (day 0)
SPECT/CT (day 3)
Spleen met. Liver met.
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-DOTATATE SPECT/CT: LMU-Reconstruction
Department of Nuclear MedicineLMU Munich
DOSE ESTIMATIONS
Day 0 Day 1 Day 2 Day 3Day 0
Organ Dose[Gy]
T1/2[h]
Tumor (spleen) 15.2 77.7
Tumor (liver) 10.5 65.7
Kidney (left) 4.2 72.2
Kidney (right) 4.5 61.5
Bone marrow 0.04 9.1 (0.5 fast)
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Radiopharmaceuticals for theranostic approaches
Department of Nuclear MedicineLMU Munich
I-131
I-131 MIBG
Ga-68 / Lu-177 somatostatine receptor ligands
Ga-68 / Lu-177 PSMA
Y-90 Ibritumomab
Y-90 Microspheres
Ra-223 Dichloride
Sm-153 EDTMP
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Radiopharmaceuticals for theranostic approaches
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED CC)]
68Ga-PSMA in clinical routine
„bench to bedside“
6/2012first patient data from Afshar-Oromieh, et al. in Heidelberg:[68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECHAfshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM.Eur J Nucl Med Mol Imaging. 2012 Jun;39(6):1085-6
since 12/2013clinical routine at our institution
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
CLİNİCAL TRANSLATİON
0 20 40 600
1
2
3
4 Tumor
TumorBackground
Background
time after injection [min]
% ID
/ g [68Ga]HBED-CC-
conjugate
[68Ga]Reference
Preclinical : LNCaPXenografts
Patient:recurrent prostate cancer
68Ga-PSMA
18F-choline
Department of Nuclear MedicineLMU Munich
Courtesy Uwe Haberkorn, Dept. of Nuclear MedicineUniversity Hospital Heidelberg
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Tracer-Uptake in human studies
Department of Nuclear MedicineLMU Munich
Courtesy Uwe Haberkorn, Dept. Nuclear MedicineUniversity Hospital Heidelberg
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Ga-68 PSMA PET / CT in metastatic prostate cancer
Department of Nuclear MedicineLMU Munich
high uptake in bone and soft tissue metastases
therapy option with Lu-177 labelled ligands
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Ga-68 PSMA PET / CT and Lu-177-PSMA therapy
Department of Nuclear MedicineLMU Munich
Ga-68 PSMA Lu-177 PSMA
Male, 54 y, 84 kg, prostate-CA, 1 x 223Ra, 1st cycle of 177Lu-PSMA (3.7 GBq)
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-PSMA wholebody planar images
Department of Nuclear MedicineLMU Munich
68Ga-PSMAPET/CT
177Lu-PSMA WB planar
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-PSMA quantitative SPECT/CT: LMU-reconstruction
Department of Nuclear MedicineLMU Munich
PET/CT LMU-Recon of SPECT & SPECT/CT (Siemens Symbia T1)
Day 1 Day 2 Day 3(68Ga-PSMA) Day 0
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-PSMA quantitative SPECT/CT: LMU-reconstruction
Department of Nuclear MedicineLMU Munich
SPECT/CT (day 0)
SPECT w/ ext. CT (day 3)
SPECT/CT (day 0)
SPECT w/ ext. CT (day 3)
Spine met. Rib met.
DOSE ESTIMATION„manual“ method
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Lu-177-PSMA quantitative SPECT/CT: LMU-reconstruction
DOSE ESTIMATION
Department of Nuclear MedicineLMU Munich
Organ Dose[Gy]
T1/2[h]
Tumor (rib) 7.6 93.6
Tumor (spine) 5.7 67.8
Kidney (left) 2.3 30.4
Kidney (right) 2.2 31.8
Bone marrow 0.04 6.4 (0.5 fast)
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of quantification / dosimetry
Department of Nuclear MedicineLMU Munich
Patient selection
Selection of radionuclide
Therapy monitoring and response
Correlation with clinical outcome
Current issues:
calibration
time and labour
manually co-registration
segmentation of relevant organ structures
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Relevance of Absolute Quantificatione.g. Samarium-153 EDTMP
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
12.12.2013 (pretherapy) 30.04.2014 (after 6 cycles Ra-223)
Therapy response following Ra-223 therapy in metastatic prostate cancer
PSA (ng/ml):Pre-therapy: 239After 6 cycles: 16,6Follow-up 3 months after 6th cycle: 9,98
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Differentiation of benign and malignant lesions
62 year old female
Breast cancer 1998
s/p ablatio mammae
s/p radiotherapy
s/p pulmonary metastasis and lungresection
CT scan in outside clinic with suspectedmetastasis of the R. inferior ossis pubisand the sacroiliac joint
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient example – pelvis – Flash 3D
Focal activity in the ischial tuberosity without explicit CT-correlate
benign? malignant?
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient example – pelvis – MRI scan
Tendinitis of the flexor muscle insertion in the ischial tuberosity
No signs for malignancy
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient example – pelvis – xSPECT
distinct focal activity; differential diagnosis, however, remains difficult
less overestimation as compared to Flash 3D
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient example – pelvis – xSPECT
Absolute quantification of uptake as a reference standard?
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Animal models – further research
Department of Nuclear MedicineLMU Munich
Siemens Intevo
170 MBq Tc-99m-DPD
SPECT parameters xSPECT bone recon 256 matrix, 64 views, 30 sec
CT parameters 16 slices 0,75 mm
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
NAME DER EİNRİCHTUNG.KANN AUCH 2 ZEİLİG SEİN
THANK YOU VERY MUCHFOR YOUR ATTENTİON!
Department of Nuclear MedicineLMU Munich
Harun IlhanDepartment of Nuclear MedicineOncology WorkgroupLMU MunichMarchioninistr. 15, 81377 MunichTel: +4989 / 7095-4646Fax: +4989 / 7095-7646Email: [email protected]
Special thanks to:Meltem Yorulmaz, Siemens MedicalMehmet Aycin, Siemens MedicalHans Vija, Siemens Medical
Peter Bartenstein, LMU MunichGuido Böning, LMU MunichAndreas Delker, LMU MunichTechnichal staff LMU MunichHans Vija, Siemens MedicalJuri Ruf, Univ. FreiburgUwe Haberkorn, Univ. Heidelberg
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient 9
63 year old male
suspected stress shielding
total hip prosthesis left 2009
s/p tibia fracture left
s/p foot ancle fracture right
Department of Nuclear MedicineLMU Munich
tracer accumulation around prosthesis stem sign for loosening
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient 9 – xSPECT vs. Flash 3D
Department of Nuclear MedicineLMU Munich
tracer accumulation as a sign for prosthesis loosening Flash 3D seems „diffuse“, whereas xSPECT is clearyl located around the prosthesis stem
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient 7
65 year old male
prostate cancer
s/p thoracal spine osteosynthesis
s/p prosthesis right hip
severe pain in lumbal spine
Department of Nuclear MedicineLMU Munich
tracer accumulation in lumbal spine malignant? inflammation? fracture?
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient 7 – lumbal spine – Flash 3D
upper and lower end plate deformity in lumbal vertebra
s/p fracture (osteoporotic)
diagnose only in awareness of CT
Department of Nuclear MedicineLMU Munich
NAME DER EİNRİCHTUNGKANN AUCH 2 ZEİLİG SEİN
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
Patient 7 – lumbal spine – xSPECT
confirmation of diagnose
all relevant information included in xSPECT
Department of Nuclear MedicineLMU Munich