Monitoring of Individuals following Acute and Chronic Exposures to Ionizing Radiation

Research Project entitled Monitoring of Individuals following Acute and Chronic Exposures to Ionizing Radiation (IAEA CRP E3.50.08 project: 17085/R0) Chang-Mo Kang, Ph.D. KIRAMS (Korea Institute of Radiological & Medical Sciences) 2013. 6. 13

Korea Institute of Radiological & Medical Sciences (KIRAMS)

Brief History 2010.7.16 Opened DIRAMS in Busan 2007.3.27 Reorganized as KIRAMS 2002.10.11 Developed Cyclotron(13MeV) first in Korea 2002.7.19 Operated CyberKnife first in Korea 2002.6.4 National Radiation Emergency Medical Center 1997.8.2 Introduced PET first in Korea 1986.11.17 Operated Cyclotron(50MeV) first in Korea 1973.2.7 Reorganized as Korea Cancer Center Hospital (KCCH) 1963.12.17 Launched as Radiation Medicine Research Institute

Organization KIRAMS Head Office of Management & Planning DIRAMS (Busan Branch) Radiological & Medical Research Institute Korea Cancer Center Hospital National Radiation Emergency Medical Center Korea Heavy Ion Med Accelerator Project Workforce & Budget Workforce : Total 1,198 (as of 2012) 2012 Budget : USD 219 million

Radiological & Medical Research Institute Korea Heavy Ion Medical Accelerator Project National Radiation Korea Cancer Center Hospital Emergency Medical Center Korea Institute of Radiological & Medical Sciences

DIVISIONS Division of Radiation Cancer Research Division of Molecular Imaging Research Division of Clinical & Translational Research Division of Radiation Effect Center of Radiation Treatment Research Radiation sensitive technique Radiation manifold technique Medical physics treatment technique for high accurate radiotherapy Disease-specific radiopharmaceuticals In vivo applications for target-specific molecular imaging & therapy Imaging-based in vivo quantitative method for preclinical & clinical study Translational research on cancer diagnosis & treatment Biomarker, new drug candidates Cancer patients database for research Radiation effect by low and high dose irradiation Biodosimetry with the use of cytogenetics Functional recovery of impaired body system using tissue engineering Toxicity evaluation of new agents for radiation treatment Radiation irradiation to SPF animal for validation test - 6 -

The 1 st cancer specialized hospital in Korea (1963) 24 clinical departments and 495 beds First-in-Korea history - Color Scanner (1967) - Gamma Camera (1969) - Cyclotron (1986) - CyberKnife (2002) - PET/CT (2003) - PET-MRI system for whole body (2009) Development of Heavy Ion Radiotherapy system (USD 183 million, 2010~16) Development of therapeutic radiopharmaceuticals (USD 85 million, 2013~16)

National Radiation Emergency Medical Preparedness Education & Training Research & Development Cooperation with IAEA & WHO

9 Title : Korea Heavy Ion Medical Accelerator Development Project (KHIMA) - Development of the first heavy ion therapy system in Korea based on the experience on Cyclotron development at KIRAMS Leading organization : Korea Institute of Radiological & Medical Sciences Location : Kijang County, Busan Metropolitan City (adjacent to DIRAMS) Project Period : 2010 ~ 2016 Project Budget : USD 183 million (195 billion KRW) Funding : KIRAMS, MEST, Busan Metropolitan City, Kijang County Total Area : 88,139m 2

10 Located in Pusan (2 nd largest city of Korea) Opened in July, 2010 - Cancer Hospital (304 beds) - Research Center

Research Project entitled Monitoring of Individuals following Acute and Chronic Exposures to Ionizing Radiation (IAEA CRP E3.50.08 project: 17085/R0)

Detailed CRP work plan (2012. 2 ~ 2016. 3). Establishment of calibration curves for 4 different biodoimetry techniques in Korean Network System: - Dicentric chromosome (DC) assay - Fluorescent In Situ Hybridization (FISH): Ch #1, 4, 8 - Micronuclei in binuclei (MNBN) assay - Premature Chromosome Condensation (PCC) assay and - Creation of a network of laboratories across Korea with the capability of providing radiation dose estimates (0, 0.1, 0.25, 0.5, 0.75, 1, 2, 4, 6Gy)

TECHNICAL REPORTS SERIES no. 405, 2001, IAEA EPR-BIODOSIMETRY 2011, IAEA IAEA Revised Manual A revised International Atomic Energy Agency (IAEA) manual was published in 2001 and 2011.

from EPR-BIODOSIMETRY 2011, IAEA

Representative Cytogenetic Assays Metaphase-based Bioassays Interphase-based Bioassays Micronuclei Assay Chemical PCC Assay PCC Assay (Mitotic-Cell Fusion) from EPR-BIODOSIMETRY 2011, IAEA

Cytogenetical Assays for Dose Assessment following Exposure to Ionising Radiation Biological end-points Spontaneous frequency 1. Dicentric Chromosome (DC) assay 2. Micronuclei in binucleated cells (MNBN) 3. Translocations using Fluorescence in situ hybridization (FISH) 4. Premature Condensed Chromosome (PCC) 0-3 / 1000 2-30 / 1000 BNC* 3-16 / 1000* 0 / 1000 * In both micronucleus and FISH based translocation assays, spontaneous frequency was found to be age dependent.

Detailed CRP work plan (2012. 2 ~ 2016. 3). Establishment of calibration curves for 4 different biodoimetry techniques: - Dicentric chromosome (DC) assay - Fluorescent In Situ Hybridization (FISH): Ch #1, 4, 8 - Micronuclei in binuclei (MNBN) assay - Premature Chromosome Condensation (PCC) assay and - Creation of a network of laboratories across Korea with the capability of providing radiation dose estimates

Dicentric chromosome (DC) assay Ring Dicentric Dicentric Tric. Tric. Dicentric Ring

Korean Standard Curve (KIRAMS) Fr equency Dose (Gy) Number of scored cells Number of chromosome with DC Frequency 0.00 5,000 9 0.002 0.10 5,000 14 0.003 0.25 5,000 41 0.008 0.50 5,000 81 0.016 0.75 5,000 168 0.034 1.00 5,000 285 0.057 2.00 3,989 886 0.222 0.25 0.20 0.15 0.10 0.05 Korean DC Curve y = 0.0024 + 0.0160D + 0.1001D 2 (+/- 0.0010 ) (+/- 0.0079 ) (+/- 0.0066 ) y = 0.0548x 2 + 0.0001x + 0.0027 R 2 = 0.9998 0.00 0.00 0.50 1.00 1.50 2.00 Do s e (G y ) (dose rate: 0.5Gy/min) by Dose estimation program for biodosimetry DoseEstimate_ver 4.1 Created by Liz Ainsbury

Fluorescent In Situ Hybridization (FISH) Ch #1, 2, 4 (all green) Ch # 1, 19 (red) / 4, 18 (green)

from EPR-BIODOSIMETRY 2011, IAEA

MN assay in binucleated cells Cytochalasin B Giemsa stained from EPR-BIODOSIMETRY 2011, IAEA

MN assay in binucleated cells Acridine orange stained MN assay with pancentromeric probe A B centromere negative centromere positive

Premature Chromosome Condensation R-PCC.(Chemical induced PCC) Cells are stained with Giemsa (left) and hybridized with human alpha satellite DNA probe according to FISH painting (right). Chemical methods of inducing PCC, using inhibitors of DNA phosphorylation, such as calyculin A or okadaic acid have also been developed. CHINESE HAMSTER OVARY (CHO) CELLS PERIPHERAL BLOOD LYMPHOCYTES CHO COLCEMID MITOTIC SHAKE OFF (METAPHASE CELLS) FICOL SEPARATION FUSE IN PEG Incubation for 1 h (Medium+Colcemid) Fusion-PCC

from EPR-BIODOSIMETRY 2011, IAEA

REAC/TS

Presentation of Gordon Livingston (REAC/TS) KIRAMS #17

Standard Technique to make the samples and to read the samples are very important.

New Korean Biodosimetry Network Laboratories B A A: KIRAMS(Korea Institute of Radiological & Medical Sciences) y = 0.0024 + 0.0160D + 0.1001D 2 (dose rate: 0.5Gy/min) (+/- 0.0010 ) (+/- 0.0079 ) (+/- 0.0066 ) B: RHRI (Radiation Health Research Institute) y = 0.00042 + 0.04484D + 0.03778D 2 (dose rate: 0.8Gy/min) C: KFDA (Korea Food and Drug Administration) D: DIRAMS C D Web-based reading the captured slide photos for network among KIRAMS(Korea Institute of Radiological & Medical Sciences), RHRI (Radiation Health Research Institute) and KFDA (Korea Food and Drug Administration)

Biodosimetry workshop for a standard technology transfer in KIRAMS 2003: Workshop was opened for a standard technology transfer to national biodosimetrist in KIRAMS. 2004. 11. 4-12: IAEA-supported National Workshop was opened for a standard technology transfer to Korean biodosimetrist with IAEA specialists whose Dr. Hayata and Dr. Darroudi in KIRAMS. 2005: Workshop was opened for a standard technology transfer to national biodosimetrist in KIRAMS. 2006: Workshop was opened for a standard technology transfer to national biodosimetrist in KIRAMS.

2007. 4. 30-5. 4: IAEA-supported Regional Workshop was opened for a standard technology transfer to 15 Asian/Pacific biodosimetrist with IAEA specialists whose Dr. Blackly, Dr. Darroudi and Dr. Zombori in KIRAMS. From NAME BANGLADESH CHINA INDONESIA IRAN, ISLAMIC REPUBLIC OF KOREA, REPUBLIC OF LEBANON MALAYSIA PAKISTAN PHILIPPINES QATAR SRI LANKA SYRIAN ARAB REPUBLIC THAILAND VIETNAM YEMEN Mr. Md. Mustafizur RAHMAN Mr. Zhijun GUO Ms. Yanti LUSIYANTI Mr. Seyed Abolghasem HAERI Mr. Jung-Eun LEE Mr. Salim CHAMMAS Ms. Noraisyah MOHD YUSOF Mr. Fazal-e- RAHIM Ms. Juana GREGORIO Ms. Leena AL-SULAITI Ms. Hiranya WILLIAMS Mr. Khaled ALMOHAMAD Ms. Darunee PEEKHUNTHOD Mr. Que TRAN Ms. Sawsan ANAAM

Programme: I.A.E.A. Ref. C7-RAS-0.050-001 Title: Regional Training Course on Biological Dosimetry Place: Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea Periods: April 30 ~ May 4, 2007

2007. 4. 30-5. 4: IAEA-supported Regional Workshop in KIRAMS

International Network for Population Triage after Multi-Casualties Biological Dosimetry in NIRS (Japan) Biological Dosimetry in Leiden Univ. (The Netherlands) MOU MOU Biological Dosimetry in AFRRI (U.S.A.) MOU plan Biological Dosimetry in RAMS (Russia) MOU plan Biological Dosimetry at KIRAMS (Korea) MOU ROD Biological Dosimetry in CMANA (China) Biological Dosimetry in REACT/TC (U.S.A.) International Network for Radiation Emergency Medical Preparedness

Thank you for your attention!