NCRP REPORT No. 83 THE EXPERIMENTAL BASIS FOR ABSORBED-DOSE CALCULATIONS IN MEDICAL USES OF RADIONUCLIDES Recommendations of the NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS Issued September 30,1985 National Council on Radiation Protection and Measurements 7910 WOODMONT AVENUE / BE'THESDA, MD. 20814 LEGAL NOTICE This report was prepared by the National Council on Radiation Protection and Meas- urements (NCRP). The Council strives to provide accurate, complete and useful infor- mation in its reports. However, neither the NCRP, the members of NCRP, other persons contributing to or assisting in the preparation of this report, nor any person acting on the behalf of any of these parties (a) makes any warranty or representation, express or implied, with respect to the accuracy, completeness or usefulness of the information contained in this report, or that the use of any information, method or process disclosed in this report may not infringe on privately owned rights; or (b) assumes any liability with respect to the use of, or for damages resulting from the use of, any information, method or process disclosed in this report. Library of Congress Cataloging in Publication Data National Council on Radiation Protection and Measurements. The experimental basis for absorbed dose calculations in medical uses of radionuclides. (NCRP report ; no. 83) "Issued September 30, 1985." Bibliography: p. Includes index. 1. Nuclear medicine-Statistical methods-Evaluation. 2. Radiation dosimetry- Evaluation. I. Title. 11. Series. R905.N38 1985 616.07'57 85-7292 ISBN 0-913392-76-6 Copyright 0 National Council on Radiation Protection and Measurements 1985 All rights reserved. This publication is protected by copyright. No part of this publication may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotation in critical articles or reviews. Preface This report reviews the status of the methods used to estimate the radiation absorbed doses to humans from internally deposited radio- nuclides with the emphasis on medical applications. Interest in and concern about internally distributed radioactive substances is not new. Most of the attention in this area has been directed to the problem of occupational exposure with lesser attention given to fallout and environmental exposure resulting from facilities using radioactivity. However, the proliferation of nuclear medicine procedures has resulted in human exposure from a variety of radio- pharmaceuticals to an increasingly large segment of the population. The internal emitter exposure may be for therapeutic or diagnostic applications. In the diagnostic situation, the upper limit of the amount of radioactivity to be administered must be determined from the radiation dose estimate. In the therapeutic situation, not only must the radiation dose necessary for the desired effect be determined, but the incidental irradiation of other organs must be considered. It is no longer satisfactory to provide radiation dose estimates for the critical organ and whole body only, but estimates of the radiation dose to the eye, the gonads, the bloodforming organs, and other organs may be needed. In this report, the emphasis is placed on comparing the results of direct measurements with calculations based on mathematical models used to estimate the parameters that enter into dose calculations. Methods are suggested which may be used to obtain good data. The history of internal radiation dosimetry is reviewed and the physical parameters and transport calculations of dosimetry are dis- cussed. Also discussed are the techniques used to measure the activity distributions in humans, and the factors which should be considered in making in-uiuoa bsorbed dose measurements. Comparisons of rneas- ured and calculated absorbed dose values in phantom animals and humans are made. A formalism is included that can be used to quantify the radioactiv- ity in irregular geometric shapes using an external measurement technique. Recommendations for further studies are also given. This report was prepared by Scientific Committee 55 on Experi- ... 111 iv / PREFACE mental Verification of Internal Absorbed Dose Calculations. Sewing on the Committee were: James S. Robertson, Chairman Department of Energy Washington, D.C. Martin J. Berger John W. Poston National Bureau of Standards Texas A and M Washington, D.C. College Station, Texas Jerry P. Jones Kenneth N. Vanek Ochsner Medical Institutions USAF Medical Center New Orleans, Louisiana Keesler Air Force Base Mississippi Katherine A. Lathrop Robert G. Zamenhof University of Chicago Tufts New England Medical Center Chicago, Illinois Boston, Massachusetts NCRP Secretariut, Thomas Fearon James T. Walker E. Ivan White The Council wishes to express its appreciation to the Committee members for the time and effort devoted to the preparation of this report. Warren K. Sinclair President, NCRP Bethesda, Maryland March 15, 1985 Contents Preface ............................................... . 1 Introduction ....................................... 1.1 Statement of the Problem ...................... 1.2 Purpose and Scope ............................. . 2 Radiation Dose Calculation Methods ................ 2.1 Historical Developments ....................... 2.2 The Marinelli Method ......................... 2.3 TheMIRDMethod ............................. 2.3.1 The Loevinger-Berman Formalism '.......... 2.3.2 The Ellett-Brownell Absorbed Fraction Calculations .............................. 2.3.3 Snyder's System of Dosimetry Calculations ... . 3 Physical Parameters and Transport Calculations in Dosimetry ......................................... 3.1 Radioactive Decay Data ....................... 3.2 Gamma-Ray Absorbed Fraction Calculations ... 3.3 Beta-Particle Absorbed Fraction Calculations . . 3.4 Beta-Ray and Electron Dosimetry in Bone ...... 3.5 Anthropomorphic Factors ...................... 3.6 Modeling ..................................... . 4 In-Vivo Measurements of Radioactivity ............. 4.1 Introduction ................................... 4.2 Area Measurements ........................... 4.3 Transverse Section Imaging ................... 4.4 Summary ..................................... . 5 In-Vivo Measurement of Absorbed Dose ............. 5.1 Introduction ................................... 5.2 General Requirements ......................... 5.3 Dose and Detector Response ................... 5.4 An Example Experiment ....................... 5.5 Human Dose Measurements .................... . 6 Comparison of Measured and Calculated Dose Values 6.1 Absorbed Dose in Phantoms .................... 6.2 Extrapolation of Biokinetic Data from Labora- tory Animals to Human Beings ............... i / CONTENTS 6.3 Absorbed Dose in Animals ..................... 6.4 Absorbed Dose in Human Beings ............... . 7 Summary and Conclusions .......................... . 8 Recommendations .................................. APPENDIX A: Formalism for the Quantification of Radio- activity in Irregular Geometric Shapes US- ing External Measurements ............... A.l Introduction ................................... A.2 Assumptions ................................... A.3 Single Detector Formalism ..................... A.4 Opposed Detector Formalism ................... A.6 Comparison of Estimated and True Activity .... A.6 Uniform Source and Exponential Attenuation . . A.7 Non-Uniform Activity Distributions ............ A.8 Final Remarks ................................ APPENDIX B: Glossary .................................. APPENDIX C: Symbols, Units and Conversion Factors .... References ............................................ NCRP ................................................. NCRP Publications ...................................... Index ................................................. 1. Introduction 1.1 Statement of the Problem Concern about the possible radiation haiards from radioactive sub- stances distributed within the human body dates from the early uses of radium in therapy. Since the advent of atomic weapons, most of the attention in this area has been directed to the problems of occupational exposure and to the real or hypothetical problems posed by fallout and other environmental sources of radioactive materials. However, the relatively recent proliferation of nuclear medicine procedures now adds exposure from a variety of radiopharmaceuticals to the radiation exposures of an increasingly large segment of the population (Frost and Sullivan, 1977; Stanford R.I., 1970). Table 1.1 lists some published estimates of the absorbed doses for a number of current nuclear medicine procedures. References to the original papers are given in the review by Robertson (1982). NCRP Report No. 70 also contains an extensive list (NCRP, 1982). While it is true that individual radiation doses are at levels regarded as being acceptable, the concept of radiation safety involves probabilistic considerations, and when large populations are exposed, even very low individual radiation doses become important considerations in assessment of potential genetic effects and in understanding the epidemiology of cancer and congenital malformations. In addition, multiple exposures of an individual to small doses are presumed to be cumulative. Accurate estimates of the radiation absorbed dose are essential for realistic appraisal of the risk- benefit equation in such situations. In diagnostic applications the radiation dose estimate is used in determining the upper limit of the amount of radioactivity that may be administered. In therapeutic applications there is not only a direct relationship between the radiation dose and the desired effect, but the incidental irradiation of other organs may impose restraints on the procedure. These requirements are reflected in the regulations that are issued by the various federal, state, and local agencies involved in the approval of the use of radioactive chemicals in research and for new clinical procedures. In applications for authorization for such uses, it is no longer satisfactory to provide radiation dose estimates 1 TABL1E.1 -Radiotion absorbed doses for current nuclear medicine ~rocedures" to Adminis- Radiation absorbed dose for listed administered activity tered \ Procedure or organ activity Total Body M",",","W Gonads Other target organs studies (mCi) ?' (3.7B xa )1 0' (.01 GY) (.O(1ra Gd) ~ ) (.0(r1a GdY) ) Organ D(o.s0e1 GbaYd)) 2 4 adrenal scan 3.9 (M) adrenal 25 (normal) 8 57 (Gushing's) IZlI NP-59 0.05 (M) adrenal 1.3 s blood pool -TC RBC or HSA - heart 1.6 2 bone scan *Tc MDP 0.34 (F) bladder wall 8.8 0 bone marrow scan ="Tc sulfur colloid 0.08 (F) liver 5.1 Z L13mIcno lloid - liver 4.3 brain scan *Tc DTPA 0.4 (F) bladder wall 12 -Tc glucoheptonate 0.4 renal cortex 4 cardiac infarct -Tc pyrophosphate 0.3 (F) bladder wall 4.8 "'TI chloride 0.38 (M) renal medulla 1.65 cisternogram 'Bgyb DTPA - brain surface 32 dacryoscintig- -TcOi - lens of eye 0.014 raphy gallium scan for tumor 67Ga citrate 2.6 5.8 2.8 (F) lower large 9 intestine for infection d?Ga citrate 1.3 2.9 1.4 (F) lower large 4.5 intestine kidney scan -Tc DTPA 0.22 - 0.27 (F) bladder wall 7.8 -Tc DMSA 0.08 - 0.11 (F) renal cortex 3.8 lUI Hippuran (+ 10% 0.0063 - 0.010 (F) bladder wall 0.33 la41) 13'1 Hippuran 0.0028 - 0.022 (P) bladder wall 1.6 liver scan ="Tc sulfur colloid 6 0.114 - 0.034 (F) liver 2.0 -Tc HIDA 20 0.18 - 0.28 (F) upper large 8.4 intestine 13'1 rose bengal 0.25 0.08 0.08 0.4 (F) upper large 9 intestine lung scan lnXe gas 15 0.020 0.026 0.021 (F) lung 0.071 lSXe gas 15 0.021 0.023 0.020 (F) lung 0.165 ="Tc microspheres 4 0.032 0.060 0.024 (F) lung 0.84 Meckel's scan BBmT~O; 5 0.060 0.095 0.090 (F) thyroid 1.00 thyroid scan ="TcO; 2 0.020 0.038 0.044 (F) thyroid 0.4 Iz3Ii odide 0.1 0.003 - 0.002 (F) thyroid 1.1 13'1 iodide 0.03 0.014 - 0.004 (F) thyroid 33 venogram BBmTm~ic rospheres 6 whole body scan 13'1 iodide 1.0 0.24 0.14 0.14 (F) stomach wall 1.7 (athyroid pa- tients) - Abbreviations: NP-59, 6-1311-iodomethyl-19-norcholesterRoBl;C , red blood cells; HSA, human serum albumin; MDP, methylene diphos- phonate; DTPA, diethylene triamine pentaacetic acetate; DMSA, dimercaptosuccinic acid; HIDA, N-(2,6-dimethylphenyl) carbamoylmethyl iminodiacetic acid. " Adapted from Robertson (1982). 4 / 1. INTRODUCTION for the whole body and a critical organ only. Estimates of the radiation dose to the eye, the gonads, the bloodforming organs, and other organs may be requested (DHEW, 1978). There are three general methods for estimating the radiation dose in human beings. These are (1)d irect measurements, (2) extrapolation from measured animal or phantom data, and (3) calculations based on mathematical models. Each of these methods has its own combination of strengths and weaknesses. In particular, radiation dose calculations are sensitive to errors in the method used and in the biological and physical input data. In human beings, the direct measurement of the absorbed radiation dose in internal organs presents severe difficulties, and very few such measurements have actually been made. Some of the problems are inherent in the physics of the situation. Others are shared by all mammalian systems, but some are unique to human studies. Most often either the locations of interest are inaccessible or the methods that are available to gain access to the site of interest are regarded as being too invasive to be acceptable. Even the clearly non-invasive methods, such as external counting, encounter obstacles associated with inconvenience or discomfort of patients. In the absence of direct measurements, estimates of the radiation- absorbed dose from internally distributed radionuclides in human beings have come to depend on calculation instead of on measurement. These calculations reflect a complex mixture of experimentally deter- mined values and theoretical considerations. For calculation of the radiation dose to one organ from a source of activity in another organ, many parameters such as the radiation absorption and scattering characteristics of intervening tissue, as well as the size and shape of both source and target organ and the biological kinetics of the distri- bution of the radioactive material have to be considered. Studies with animals and phantoms are free from some of the difficulties that are encountered in attempting to measure the radia- tion dose parameters in human beings, but these studies have other inherent weaknesses. To the degree that the animal models may simulate the biochemical and physiological characteristics of human beings, they are useful in determining some of the parameters of the kinetics of distribution of a given radioactive substance. In extrapo- lating such data to human beings, however, a correction for the time scale usually must be introduced, and the scaling factor may be difficult to determine. Anthropomorphic phantoms are useful for simulating the spatial relationships among the body organs, but typically have no ability to reproduce the kinetic parameters. In phantoms that are to
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