Radioactive Drug Research
Committee
December 11, 2007
New York, New York
Orhan H Suleiman
Richard Fejka
Alex Gorovets
Office of New Drugs
Office of Oncology Drug Development
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Radiation Dosimetry
RDRC Meeting
New York City
December 11, 2007
Orhan H Suleiman, MS, PhD, FAAPM
Senior Science Policy Advisor
Office of New Drugs
Office of Oncology Drug Development
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Radiation Dosimetry
 RDRC
Dose Limits
 Diagnostic Doses
 Radiotherapeutics
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RDRC Radiation Dose Limits*
Organ or System
Single Dose
Whole body
Active blood-forming
organs
Lens of the eye
Gonads
Other organs
0.03 Sv (3 Rem)
0.05 Sv (5Rem)
0.03 Sv
0.03 Sv
0.03 Sv
0.05 Sv
0.05 Sv (5 Rem)
0.05 Sv (5 Rem)
0.05 Sv (5 Rem)
0.15 Sv (15 Rem)
(3 Rem)
(3 Rem)
(3 Rem)
(5 Rem)
Annual and Total Dose
Based on 1975 Nuclear Regulatory Commission’s occupational dose limits
*21 CFR 361.1 (b) (3)
Radiation doses from x-ray procedures that are part of the research study shall
also be included.
For research subjects under 18 years of age at his last birthday, the radiation
dose does not exceed 10 percent of adult dose.
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How do I determine the radiation dose
from radiopharmaceutical?
Organ doses and whole body doses (as specified in
21 CFR 361.1) can only be estimated using standard
adult and child mathematical reference models.
For radionuclides you should use methods of the:
Medical Internal Radiation Dosimetry (MIRD) committee of the
Society of Nuclear medicine (SNM)
http://interactive.snm.org/index.cfm?PageID=2199&RPID=1372
International Commission on Radiological Protection (ICRP)
Publications. www.icrp.org
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Biodistribution

If there is insufficient human biodistribution or
pharmacokinetic data, absorbed dose
calculations may be based on animal data.

However- FDA recommends that the RDRC
investigators validate with human data on the
first 5-10 subjects and begin using the human
biodistribution data for subsequent calculations.
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How do I determine the radiation dose
from x-rays?
Radiation doses from associated x-ray procedures that are part
of the research study shall also be included.
For x-ray, and CT:
Food and Drug Administration (X-ray)
http://www.fda.gov/cdrh/ohip/organdose.html
British Health Protection Agency (CT)
http://www.hpa.org.uk/radiation/
http://www.hpa.org.uk/radiation/publications/software/index.htm
German national Research Center for Environemtn and
Health(Gesellschaft fur Strahlen-und-Umweltforschung (GSF)
http://www.gsf.de/index_en.php
Finnish Radiation and Nuclear Safety Authority (STUK)
http://www.stuk.fi/sateilyn_kayttajille/ohjelmat/PCXMC/en_GB/introduction/
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How do I determine the radiation dose
using most recent models?
Exciting research and activity in this area, with many free, and
linked websites, along with commercial services, for
calculating organ doses from a variety of radiation sources.
Two links which will serve as a gateway to much of the ongoing
research are:
Radiation Dose Assessment Resource (RADAR)
http://www.doseinfo-radar.com/RADARphan.html
Consortium of Computational Human Phantoms (CCHP)
http://www.virtualphantoms.org/
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Patient Phantoms
Stylized versus Voxel
MIRD stylized phantoms
Voxel phantoms
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Patient Phantoms
UF 9-month male phantom
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Patient Phantoms
UF Pediatric Phantom Series
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Stylized vs Voxel Phantom
External dosimetry
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Image-Based Advances in Skeletal Dosimetry
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Radiation Dose
 Administered


dose
Mass dose
Activity- MBq (mCi)
 Radiation Absorbed

mGy (rads)
 Equivalent

Dose
Dose (Dose equivalent)
mSv (mRem)
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Radiation Dose- what to report?
The fundamental radiation unit of dose we need to know
is the organ (tissue) dose. 21 CFR 361.1 also requires
reporting of the whole body.
It is essential to know the actual organ dose estimates,
especially for the organs which receive the highest
doses.
Effective dose, E, will be acceptable as nominally
equivalent to the whole body dose.
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Effective Dose ~ Whole Body Dose
The effective dose (E) is the sum of the
weighted equivalent doses in all the
tissues and organs of the body.
E = ΣT WTHT
Where HT is the individual tissue or organ dose for tissue
T,
And WT is the weighting factor for tissue T,
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Tissue Weighting Factors (wt)
Organ (Tissue)
ICRP
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ICRP
60
ICRP
Draft - 2004
Gonads
Breast
0.25
0.15
0.20
0.05
0.05
0.12
Red BM, lung
Thyroid
0.12
0.03
0.12
0.05
0.12
0.05
Bone surfaces
Colon, stomach
Bladder, liver, esophagus
Skin
0.03
NC
NC
NC
0.01
0.12
0.05
0.01
0.01
0.12
0.05
0.01
Salivary glands, brain
Remainder
Total
NC
0.30
1.00
NC
0.05
1.00
0.01
0.10
1.00
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In summary
 Use
the correct methodologies
 Calculate the individual organ doses from
all sources, including x-ray.
 Use human biodistribution data.
 Understand the different dose metrics.
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Any questions?
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