‘monitoring of individuals - human health campus · pdf filebrief history 2007.3.27 ......

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)

1963.12.17 Launched as Radiation Medicine Research Institute

1973.2.7 Reorganized as Korea Cancer Center Hospital (KCCH)

1997.8.2 Introduced PET first in Korea

2002.6.4 National Radiation Emergency Medical Center

2002.7.19 Operated CyberKnife first in Korea

2002.10.11 Developed Cyclotron(13MeV) first in Korea

2010.7.16 Opened DIRAMS in Busan

Brief History

2007.3.27 Reorganized as KIRAMS

1986.11.17 Operated Cyclotron(50MeV) first in Korea

Organization

Radiological & Medical

Research Institute

DIRAMS (Busan Branch)

Korea Cancer

Center Hospital

National Radiation

Emergency Medical Center

KIRAMS

Korea Heavy Ion Med

Accelerator Project

Head Office of Management & Planning

Workforce : Total 1,198 (as of 2012)

2012 Budget : USD 219 million

Workforce & Budget

Korea Cancer

Center Hospital National Radiation

Emergency Medical Center

Korea Heavy Ion

Medical Accelerator Project

Korea Institute of Radiological

& Medical Sciences

Radiological & Medical

Research Institute

Division of Radiation

Cancer Research

Radiation sensitive technique

Radiation manifold technique

Medical physics treatment technique for high accurate radiotherapy

Division of Molecular

Imaging Research

Disease-specific radiopharmaceuticals

In vivo applications for target-specific molecular imaging & therapy

Imaging-based in vivo quantitative method for preclinical & clinical study

Division of Clinical &

Translational Research

Translational research on cancer diagnosis & treatment

Biomarker, new drug candidates

Cancer patients database for research

Division of Radiation

Effect

Radiation effect by low and high dose irradiation

Biodosimetry with the use of cytogenetics

Functional recovery of impaired body system using tissue engineering

Center of Radiation

Treatment Research

Toxicity evaluation of new agents for radiation treatment

Radiation irradiation to SPF animal for validation test

DIVISIONS

- 6 -

The 1st 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)

Cooperation with

IAEA & WHO

Education & Training

Research &

Development

National Radiation

Emergency Medical

Preparedness

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 : 88,139m2

Located in Pusan (2nd largest city of Korea)

Opened in July, 2010

- Cancer Hospital (304 beds)

- Research Center

10

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)

• A revised International Atomic Energy Agency (IAEA) manual

was published in 2001 and 2011.

IAEA Revised Manual

EPR-BIODOSIMETRY 2011, IAEA TECHNICAL REPORTS SERIES no. 405, 2001, IAEA

from EPR-BIODOSIMETRY 2011, IAEA

Representative Cytogenetic Assays

Chemical PCC

Assay

Interphase-based

Bioassays

Metaphase-based

Bioassays

PCC Assay

(Mitotic-Cell Fusion)

Micronuclei

Assay

from EPR-BIODOSIMETRY 2011, IAEA

Cytogenetical Assays for Dose Assessment

following Exposure to Ionising Radiation

1. Dicentric Chromosome (DC) assay

2. Micronuclei in binucleated cells (MNBN)

4. Premature Condensed Chromosome (PCC)

3. Translocations using

Fluorescence in situ hybridization (FISH)

0-3 / 1000

2-30 / 1000 BNC*

0 / 1000

Spontaneous frequency Biological end-points

* In both micronucleus and FISH based translocation assays,

spontaneous frequency was found to be age dependent.

3-16 / 1000*

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

Ring

Dicentric

Dicentric

Dicentric

Tric.

Tric.

Korean Standard Curve (KIRAMS)

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

Korean DC Curve

y = 0.0548x 2 + 0.0001x + 0.0027

R 2 = 0.9998

0.00

0.05

0.10

0.15

0.20

0.25

0.00 0.50 1.00 1.50 2.00

Dos e (Gy )

Fre

que

ncy

y = 0.0024 + 0.0160D + 0.1001D2 (+/- 0.0010 ) (+/- 0.0079 ) (+/- 0.0066 )

(dose rate: 0.5Gy/min)

DoseEstimate_ver 4.1 Created by Liz Ainsbury

by Dose estimation program for biodosimetry

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

Fluorescent In Situ Hybridization (FISH)

Ch #1, 2, 4 (all green)

Ch # 1, 19 (red) / 4, 18 (green)

from EPR-BIODOSIMETRY 2011, IAEA

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

MN assay in binucleated cells

Cytochalasin B

Giemsa stained

from EPR-BIODOSIMETRY 2011, IAEA

MN assay in binucleated cells

Acridine orange stained

A

centromere negative

B

centromere positive

MN assay with pancentromeric probe

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

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.

Premature Chromosome Condensation

FICOL SEPARATION FUSE IN PEG

LYMPHOCYTES CHO

CHINESE HAMSTER

OVARY (CHO) CELLS

COLCEMID

MITOTIC SHAKE OFF

(METAPHASE CELLS)

Fusion-PCC Incubation for 1 h

(Medium+Colcemid)

PERIPHERAL BLOOD

from EPR-BIODOSIMETRY 2011, IAEA

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

and harmonize

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

A

C

B

D

A: KIRAMS(Korea Institute of Radiological & Medical Sciences)

y = 0.0024 + 0.0160D + 0.1001D2 (dose rate: 0.5Gy/min)

(+/- 0.0010 ) (+/- 0.0079 ) (+/- 0.0066 )

B: RHRI (Radiation Health Research Institute)

y = 0.00042 + 0.04484D + 0.03778D2 (dose rate: 0.8Gy/min)

C: KFDA (Korea Food and Drug Administration)

D: DIRAMS

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)

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.

Biodosimetry workshop for a standard technology transfer in KIRAMS

From NAME

BANGLADESH Mr. Md. Mustafizur RAHMAN

CHINA Mr. Zhijun GUO

INDONESIA Ms. Yanti LUSIYANTI

IRAN, ISLAMIC REPUBLIC OF Mr. Seyed Abolghasem HAERI

KOREA, REPUBLIC OF Mr. Jung-Eun LEE

LEBANON Mr. Salim CHAMMAS

MALAYSIA Ms. Noraisyah MOHD YUSOF

PAKISTAN Mr. Fazal-e- RAHIM

PHILIPPINES Ms. Juana GREGORIO

QATAR Ms. Leena AL-SULAITI

SRI LANKA Ms. Hiranya WILLIAMS

SYRIAN ARAB REPUBLIC Mr. Khaled ALMOHAMAD

THAILAND Ms. Darunee PEEKHUNTHOD

VIETNAM Mr. Que TRAN

YEMEN Ms. Sawsan ANAAM

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.

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 Radiation Emergency Medical Preparedness

International Network for Population Triage after Multi-Casualties

Biological Dosimetry

at KIRAMS

(Korea) Biological

Dosimetry

in Leiden Univ.

(The Netherlands)

Biological

Dosimetry

in AFRRI

(U.S.A.)

Biological

Dosimetry

in REACT/TC

(U.S.A.)

Biological

Dosimetry

in CMANA

(China)

Biological

Dosimetry

in NIRS

(Japan)

MOU MOU

MOU ROD

Biological

Dosimetry

in RAMS

(Russia)

MOU plan MOU plan

Thank you

for your attention!