THE LATIN AMERICAN BIOLOGICAL DOSIMETRY ...2010 Aragua, Venezuela 2014 Ventanilla, Peru 2014 Mexico...

The foundational basis of the Latin American Biological Dosimetry Network (LBDNet): mission, partners, concept of operation,

network capabilities, activation during an emergency response

Marina Di Giorgio & *Omar García Autoridad Reguladora Nuclear. Buenos Aires - Argentina

*Centro de Protección e Higiene de las Radiaciones. La Habana - Cuba [email protected]

[email protected]

ARADOS Annual Meeting, Beijing , 6-8November 2019

mailto:[email protected]

mailto:[email protected]

The quantification of unstable chromosome aberrations (dicentrics) is the

most reliable biological method for estimating individual whole-body doses

of recent, acute, largely uniform exposures to external irradiation/internal

irradiation with radionuclides such as 137Cs and 3H that distribute uniformly

in the body

CYTOGENETIC DOSIMETRY (BIOLOGICAL DOSIMETRY)

BIODOSIMETRY (role):

1. Radiological/nuclear accidents: to guide medical treatment (emergency

response)

2. Radiation protection: workers with personal dosimetry above the

permitted limits

3. Clinical applications: e.g. to support treatment decisions in patients with

differentiated thyroid carcinoma under 131I therapy; BM dose

assessment, to avoid myelotoxicity threshold

4. Long-term health risk studies following radiation exposure (radiation

epidemiology)-FISH and EPR (retrospective dose)

It has been observed that victims of accidental overexposuresshow better chance of survival if they receive medical treatmentearly

The increased risk of scenarios involving mass casualties hasstimulated the development of tools that would help the medicaldoctors to treat victims

The Biological Dosimetry has become a routine test to estimatethe dose, contributing with physical and clinical dosimetry

One of the existing strategies to afford mass casualty events is theuse of cytogenetic networks to enlarge the capabilities for rapidtriage and reference dose assessment, sending blood samples (orpellets), slide preparations or electronically transmitted images

The Latin American Biological Dosimetry Network (LBDNet)

BACKGROUND

Biological Dosimetry is a necessary support forNational Radiation Protection Programs andEmergency Response Schemes

Retrospectively, before LBDNet foundation in 2007, atleast 24 significant accidents had been reported in theLatin American Region (1962-2007) reinforcing theneed for a biodosimetric response generated in theRegion itself

In the framework of the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency- IAEA and / or bilateral agreements

Goiania, Brazil1987El Salvador1989Yanango, Peru2000

Cochabamba, Bolivia2002

Nueva Aldea, Chile2005

Radiological incident in Venezuela2005 - 2006

2007 LBDNet

Ecuador y El Salvador2009

Aragua, Venezuela2010

Ventanilla, Peru2014

Mexico2014

Biological dosimetry assistance in radiological accidents occurred in the Region before an after LBDNet

The participation in: Goiania (Brazil), ElSalvador, Cochabamba (Bolivia), NuevaAldea (Chile) radiological accidents, andVenezuela incidents, were actions thatproved an improvement in organizationand response in cases of suspected orconfirmed overexposures to IR occurred inthe Latin American Region

These antecedents showed that thelaboratories had reached a commonbackground level that allowed them toformalize a BD network (in 2007) forcooperation purposes, aiming at workingin integration with National RadiologicalEmergency Response Systems and to otherinternational assistance programs

BACKGROUND

LBDNet Background


The LBDNet was formally founded in 2007

Main topics considered in the foundational document of the LBDNet are presented here.

Previous attempts: 1990 - ARCAL I.

1996- Radiation Protection Societies.

1999-ARCAL XXXVII project.

2006-Regional Workshop on the ISO 19238.

Havana Cuba. October 29 - November 2 – 2007. Regional Workshop on TECDOC-260 & 405, and ISO 19238:2004 . Regional IAEA project “Strengthening of National Capabilities for Response to Radiation Emergencies”(RLA/9/054)

The LBDNet was established in 2007 in the frame of the IAEA’sTechnical Cooperation Project RLA/9/054 Strengthening NationalSystems for Preparedness and Response to Nuclear and RadiologicalEmergencies with the purpose of mutual assistance in case of aradiation emergency.

Organization and activities within the LBDNet are performed asrecommended by the ISO 21243 standard

NETWORKING

The Latin American Biological Dosimetry Network (LBDNet)

LBDNet Mission


The LBDNet mission is to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American region

LBDNet Objectives


1. To strength the service capacities of Biological Dosimetry laboratories existing in the region to provide an early biodosimetric response for mutual assistance, integrated to the National Radiological Emergency Plans

1. To provide support to other Latin American countries that do not have biological dosimetry laboratories

2. To work cooperatively and articulately with other international networks.

Besides, the LBDNet support inter-comparison exercises to keep

standard goals on biological dosimetry preparing and sending

processed blood samples for cytogenetic analysis or uploading

cytogenetic images to the internet network created to share and

discuss results obtained by any laboratory of the Network

OBJECTIVES

LBDNet Partners


* Laboratories from Bolivia, Costa Rica, Paraguay, Venezuela, Ecuador and an associated laboratory from Brazil

recently joined the LBDNet activities.

• The LBDNet is a consortium of reference laboratories

• The integration is based on a voluntary and consensual participation of laboratories qualified in biological dosimetry

• Representation of laboratories is institutional, not personal

• All the laboratories of the network are working within national emergency response systems

LBDNet Concept of operation


In normal situations each laboratory of the network has the same hierarchical level

During emergency situations the activities within the LBDNetare performed as recommended by the ISO 21243 guidelines

The laboratories of the LBDNet give support to national radiation-protection programs and emergency response schemes

NETWORK ACTIVATION AND MAINTENANCE

Network design

At the national level, the laboratories work within national emergencyresponse systems

At the international level, the network cooperates with the IAEA Incidentand Emergency Centre (IEC) in the frame of the Convention of EarlyNotification of a Nuclear Accident and the Convention on Assistance inthe Case of a Nuclear Accident or Radiological Emergency, and with otherassistance systems such as REMPAN/WHO-Global BiodosimetryLaboratories Network

The network is opened for collaboration with laboratories in othercountries in the region and from other regions, as well as forcollaboration with other national and regional networks

IN NORMAL SITUATION:

• Each laboratory of the network has the same hierarchical level(consortium of reference laboratories) and interact amongthem through training, exercises, intercomparisons and drills.These activities should involve technical, communication andorganization-activation aspects

NETWORK ACTIVATION


IN EMERGENCY

• A reference (coordinating) laboratory and associatedlaboratories. Associated laboratories belonging to the LBDNetcould be from inside as well as outside the country

• Associated laboratories inside the country: Example ofArgentina case: the development of the technical competenceof a laboratory non related with our institution is in process

IN EMERGENCY

• Associated laboratories outside the country: are those defined inthe consortium of the network laboratories

• The concept of reference or coordinating laboratory andassociated laboratory is dynamic; a laboratory acting as areference in a particular accidental situation while as anassociated in other cases

• Habitually, the network laboratory of the country where theaccident has occurred becomes the reference laboratory for thatemergency. It is primarily responsible for the communicationwith the national emergency organizations and with otherinternational assistance systems, and for issuing dose estimationresults


IN EMERGENCY

• The reference laboratory is responsible for network activationand calls for the collaboration of the network associatedlaboratories when the number of cases to be examined exceedsits operative capacity

• When the decision to activate the network is made, thereference laboratory, where the accident has occurred, becomesthe focus for the communication among the network members,except that due to operative reasons the laboratory delegatesthis function to an associated one

• In cases where the event takes place in a country without abiodosimetry laboratory, the emergency officials may contactany other of the laboratories in the network, which will becomethe reference laboratory




Cases exceed operational capabilities

National Emergency Response Systems

Accident

Country with BD Laboratory Country without BD Laboratory

RANET IAEA-IEC WHO-BioDoseNet

Bilateral

Agreement

ARN

Argentina

Define

Coordinating laboratory

LBDNet Activation

Network laboratories

Results & Reports

NETWORK ACTIVATIONIN EMERGENCY

Argentina’s lab. is the region’s laboratory registered under IAEA- RANET system (since 2008) and accredited under ISO17025:2017 and ISO19238:2014 standards



The network is activated when the number of cases for examination is above the coordinating laboratory’s workload

The network uses the activation and communication mechanisms of the National Emergency Response Systems

Biological dosimetry using the dicentricassay

Technical procedures based on ISO 19238 and IAEA’s manual on biodosimetry

LBDNet Tools

At present, the response of the network in an emergency situation involves the use of the dicentric analysis

The technical procedures status of the region wasevaluated and the conformity to ISO 19238 and IAEA’sEPR-Biodosimetry 2011 was determined

LBDNet Tools

Most of the laboratories have implemented other establishedtechniques for biodosimetry such as Cytokinesis blocked micronucleusassay, FISH technique, PCC-ring induction and the H2AX assay

LBDNet Tools

All LBDNet’s laboratories constructed its own calibration curves fordicentric assay using gamma radiation

The number of calibration curves for different radiation qualities perlaboratory fluctuated from one (for gamma radiation) to 4 (e.g. 20MeV α particles, 6 MeV and 15 MeV photons are available in onelaboratory of the region for dicentric technique- Argentina)

The mechanisms for the activation of the network:

• To use the activation and communication mechanisms of theNational Radiological or Nuclear Emergency Response System,profiting from the infrastructure and focal points alreadyexistent in each country

• The focal point in each country is responsible for the activationof the network

This activation could be initiated by:

1. IAEA-IEC, in the frame of the Convention of Early Notificationof a Nuclear Accident and the Convention on Assistance inthe Case of a Nuclear Accident or Radiological Emergency

2. bilateral agreements between the Region countries


• The standardization of the techniques to be involved, in orderto pool data in a combined response, when a large number ofpersons must be evaluated

• The information exchange and training organization betweennetwork staffs for all scientific and technical questions relatedto the network tasks

• All these parameters have to be established and maintainedthrough meetings of consensus, organized regularly. It isproposed at least every 2 years

Preparedness and maintenance of the laboratory network for theresponse

Cytogenetic analysis for dose estimation is performed at thephysician’s request. Selection of the cases to be examined ismade by discussion among physicians, experts in biologicalDosimetry, and scene managers

The reference laboratory and the network laboratories discussthe details of work distribution: to establish what laboratorieswill participate, the number of evaluations that will beperformed by each laboratory, the way in which the data will beinformed, etc.

An informed written consent (original for the referencelaboratory and copy for the associated ones) has to be submittedfrom each individual or a treating physician, as applicable, priorto blood sampling. Special care has to be taken to protect privacythorough the assignment

OPERATION

The reference laboratory itself organizes the blood sampling anddispatching of specimens to the partners when and if possible,or assigns another suitable laboratory to take over. To minimizedelay, local/regional hospital (treating the patients) maydispatch blood specimens directly to the foreign networklaboratories. These action would be supervised and coordinatedby members of UNDP of the own country to facilitate thesending

An alternative procedure may be adopted by the referencelaboratory to process the specimens and send fixed cellsuspensions or microscope slides to the network partners. Thesealternatives would be previously agreed on by a discussionamong partners

OPERATION

Partners will also agree if the aberration scoring is to beperformed in each laboratory or one local associated laboratoryjust help with culturing and then giving fixed cell suspensions ormicroscope slides to the network partners

It will be established by consensus of partners the cytogenetictechniques to be applied (dicentric assay and the convenience toinclude or not micronucleus assay). In the case of an accidentwith mass casualties the cytogenetic triage criteria will beapplied: to evaluate 50 metaphases per patient or to stopsooner if 30 dicentrics have been found; and to evaluate 200binucleated cells for micronucleus assay

OPERATION

The associated laboratories will send the raw data and thedistribution of aberrations to the reference laboratory. They willalso be able to send the dose estimates, adjusted whennecessary for dose protraction or heterogeneity, obtained fromtheir own calibration curves, which should be specified

The reference laboratory receives the results from the networkpartners and acts as the central point of communication withthe physicians

Following the review of the informed data, medical staff mayselect the patients of major clinical interest for increased cellscoring in order to improve statistical uncertainties on doseestimation and better discrimination of homogeneity or inhomogeneity on dose distribution, according to ISO 19238standard

OPERATION

Operational capabilities* of LBDNet


Human resources:• From 1 up to 5 specialists/laboratory

Experience in cytogenetic:• First BD Lab founded in 1968• Majority of members more than 20 years of

experience

Calibration curves (dicentric assay ):• In all LBDNet’s laboratories using gamma

radiation • For different radiation qualities up to 4 in

one laboratory of the regionEquipment:• Only 4 labs (out of 7) had automated

metaphase localization and capture system to assist in the analyses (+2 New labs)

* Regular update

Quality Management Systems: • One laboratory accredited under ISO

17025:2005 (ARN-Argentina) • Another has implemented the standard

(CPHR-Cuba)

LBDNet activities


First intercomparison (1)*

• Organized and performed in the framework of the IAEA Regional Project - RLA/9/054

• 8 Latin American laboratories and 6 from Europe

• Significant aspect: the results were assessed by applying a statistical approach based on robust methods -ISO standards (ISO 13528/ 2005 & ISO/IEC 43-1 /1997)

(1) Biological Dosimetry Intercomparison Exercise: An evaluation of Triage and Routine Mode Results by Robust Methods Radiation Research 175, 638–649 (2011).

* First regional intercomparison published in 1995 Mut . Res 327 (33-39) ARCAL I Project

LBDNet activities


Second intercomparison (2)

• Organized and performed in in the framework IAEA Regional Project -RLA/9/054

• 7 LBDNet´s laboratories , 3 associated laboratories and 3 from Europe

• Significant aspect: Dicentric telescoringand results evaluated by robust methods (ISO 13528/ 2005 & ISO/IEC 43-1 /1997).

(2) Interlaboratory comparison of dicentric chromosome assay using electronically transmitted images. Radiat Prot Dosimetry; 154, 18–25 (2013).

LBDNet activities


Additionally the LBDNet has organized :

• ShipEx -1 (Peru -2009)-Joint IAEA, PAHO and WHO International Exercise (shipment of blood samples )

• Two harmonization workshops to standardize scoring criteria for the PCC-r assay

• PCC-r Intercomparison exercise (unpublished -results under discussion)

• Training exercise using the BioDoseNetimage repository

Conclusions


The LBDNet activities allowed the region to develop tools for an effective and coordinated response in cases of radiological or nuclear emergencies

The LBDNet and the future:

• Integration of research activities• Introduction of other techniques• Periodic intercomparison• Regular funding• Strong links with national and

international emergency response systems

CONCLUSIONS

• The experience gained by intercomparisons, training activities,courses and meetings has allowed the region to be prepared toproduce an effective and coordinated response in cases ofradiological or nuclear emergencies. Nevertheless, improvementsin scoring criteria, sustainable integration of research activities,introduction of other techniques for the interpretation ofdifferent overexposure scenarios, continuity of training programsand periodic intercomparison exercises are necessary to maintainthe operative capacity of the network

CYTOGENETIC DOSIMETRY (BIOLOGICAL DOSIMETRY)

FUTURE CHALLENGES ON THE BIODOSIMETRY ROLE IN THE LBDNet:

1. Radiological/nuclear accidents: to guide medical treatment (emergency

response)

2. Radiation protection: workers with personal dosimetry above the

permitted limits

3. Clinical applications: e.g. to support treatment decisions in patients with

differentiated thyroid carcinoma under 131I therapy; BM dose

assassment, to avoid myelotoxicity threshold

4. Long-term health risk studies following radiation exposure (radiation

epidemiology)-FISH and EPR (retrospective dose)

5. Development of biomarkers

6. Evaluation of individual radiosensitivity

Acknowledgments/ Funding


The LBDNet activities were supported by the International Atomic Energy Agency Projects (Technical Cooperation programs)

RLA9054,RLA9061, RLA9074 and RLA9085

Strengthening National Systems for Preparedness and Response to Nuclear and Radiological Emergencies.

The last network meeting was supported with funding by the European Union.

“The views expressed in this presentation do not necessarily reflect the views of the European Commission..”


Additional information

Gracias / Thank You

THE LATIN AMERICAN BIOLOGICAL DOSIMETRY ...2010 Aragua, Venezuela 2014 Ventanilla, Peru 2014 Mexico...

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