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

1

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

2

Radiation Dosimetry

 RDRC Dose Limits  Diagnostic Doses  Radiotherapeutics 3

RDRC Radiation Dose Limits* Organ or System Single Dose Annual and Total Dose Whole body Active blood-forming organs Lens of the eye Gonads Other organs 0.03 Sv (3 Rem) 0.03 Sv (3 Rem) 0.03 Sv (3 Rem) 0.03 Sv (3 Rem) 0.05 Sv (5 Rem) 0.05 Sv (5Rem) 0.05 Sv (5 Rem) 0.05 Sv (5 Rem) 0.05 Sv (5 Rem) 0.15 Sv (15 Rem) 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.

4

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

5

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.

6

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/

7

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/

8

Patient Phantoms Stylized versus Voxel MIRD stylized phantoms Voxel phantoms

9

Patient Phantoms UF 9-month male phantom

10

Patient Phantoms UF Pediatric Phantom Series

11

Stylized vs Voxel Phantom External dosimetry

12

Image-Based Advances in Skeletal Dosimetry

13

Radiation Dose

 Administered dose  Mass dose  Activity- MBq (mCi)  Radiation Absorbed Dose  mGy (rads)  Equivalent Dose (Dose equivalent)  mSv (mRem) 14

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. 15

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

= Σ T

W T H T Where H T

T, is the individual tissue or organ dose for tissue

And W T

is the weighting factor for tissue T, 16

Tissue Weighting Factors (w

t

)

Organ (Tissue) ICRP ICRP ICRP 26 60 Draft - 2004 Gonads Breast 0.25

0.15

0.20

0.05

0.05

0.12

Red BM, lung Thyroid Bone surfaces Colon, stomach Bladder, liver, esophagus Skin Salivary glands, brain Remainder Total 0.12

0.03

0.03

NC NC NC NC 0.30

1.00

0.12

0.05

0.01

0.12

0.05

0.01

NC 0.05

1.00

0.12

0.05

0.01

0.12

0.05

0.01

0.01

0.10

1.00

17

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.

18

Any questions?

19