Table Of ContentNCRP REPORT No. 70
NUCLEAR MEDICINE-FACTORS INFLUENCING
THE CHOICE AND USE OF RADIONUCLIDES
IN DIAGNOSIS AND THERAPY
Recommendations of the
NATIONAL COUNCIL ON RADIATION
PROTECTION AND MEASUREMENTS
Issued June 1, 1982
First Reprinting February 28,1992
National Council on Radiation Protection and Measure-
men ts
7910 WOODMONT AVENUE / BETHESDA, MD 20814
LEGAL NOTICE
This report was prepared by the National Council on Radiation Protection and Mea-
surements (NCRP). The Council strives to provide accurate, complete and useful
information 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
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any information, method or process disclosed in this report.
Copyright O National Council on Radiation
Protection and Measurements 1982
All rights reserved. This publication is protected by copyright. No part of this publication
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Library of Congress Catalog Card Number 81-84121
International Standard Book Number 0-913392-57-x
International Standard Serial Number ISSN 0083-209x
Preface
.
This report addresses the many factors which influence the choice
of the proper radiopharmaceutical drug product for the diagnosis or
treatment of a specific disease or condition in a human subject.
The Report examines the historical factors that influence the choice
of radionuclides, the factors that influence the localization of radio-
nuclides in tissues, the factors that influence the choice of instruments,
and includes an evaluation of the nuclear medicine procedures that
could be selected and their clinical usefulness. In examining these
factors the desirable characteristics of the radiopharmaceutical drug
products and of the measurement systems are identified. The methods
of dose determination and the assumptions used in determination of
dose are developed. There is also a section on radiation effects. A
chapter on guidelines for procedures in nuclear medicine and some
general and specific recommendations for protection of patients con-
clude the body of the text. Guidelines for the clinical evaluation of
radiopharmaceutical drugs which were developed by the Food and
Drug Administration's Radiopharmaceutical Advisory Committee are
set out in Appendix A. Appendix B provides radiation absorbed dose
estimates for many radiopharmaceutical drug products.
The Council has noted the adoption by the 15th General Conference
of Weights and Measures of special names for some units of the
Systbme International #Unites (SI) used in the field of ionizing
radiation. The gray (symbol Gy) has been adopted as the special name
for the SI unit of absorbed dose, absorbed dose index, kema, and
specific energy imparted. The becquerel (symbol Bq) has been adopted
as the special name for the SI unit of activity (of a radionuclide). One
gray equals one joule per kilogram; and one becquerel is equal to one
second to the power of minus one. Since the transition from the special
units currently employed-rad and curie-to the new special names is
expected to take some time, the Council has determined to continue,
for the time being, the use of rad and curie. To convert from one set of
units to the other, the following relationships pertain:
1 rad = 0.01 J kg-' = 0.01 Gy
1 curie a 3.7 x 1010 8-I = 3.7 X 10'' Bq (exactly).
iii
iv / PREFACE
Serving on Scientific Committee 32 on Administered Radioactivity
during the preparation of this report were:
A. Bertrand Brill, Chairman
Medical Department
Brookhaven National Laboratory
Upton, LI, New York
Members
S. James Adelstein Robert N. Beck
Harvard Medical School The Franklin McLean Me-
25 Shattuck Street morial Research Institute
Boston, MA 950 East 59th Street
Chicago, IL
Roger J. Cloutier Mary Rose Ford
Oak Ridge Associated Universities Oak Ridge National Labora-
P. 0.B ox 117 tory
Oak Ridge, TN P. 0.B ox X
Oak Ridge, TN
R. Eugene Johnston Paul Numerof
Division of Nuclear Medicine 10 Ryan Road
University of North Carolina Edison, NJ
Chapel Hill, NC
George V. Taplin (Deceased) Saul Winchell
Nuclear Medicine Research Lab Medi-Physics Inc.
UCLA Dept of Radiology 5855 Christie Avenue
Los Angeles, CA Emeryville, CA
Consultants
William G. Myers Suresh Srivastava
The Ohio State University Hospitals Brookhaven National Labo-
Columbus, Ohio ratory
Upton, LI, New York
NCRP Secretariat, James A. Spahn, Jr.
The Council wishes to express its gratitude to the members of the
Committee for the time and effort devoted to the preparation of this
report.
Warren K. Sinclair
President, NCRP
Bethesda, Maryland
7 August 1981
CONTENTS
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . , . . . , . . . .
1. Decision Making in Nuclear Medicine . . . . . . . . . . . . . . .
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . - - . . , . . . . . . . .
2. Decision-Making Considerations in the Choice of
Radiopharmaceutical Drug Products . . . . . . . . . . . . . . . .
2.1 Historical Factors Influencing the Use of Radionu-
clides in Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2 Desirable Characteristics of Radioactive Diagnostic
Drugs . . . . . . . . . . . . . . . . . . . , . , , . . . . . . ... . . . . . . . . . . . . .
2.2.1 Optimum Radionuclide Characteristics Relative to
Available Detection Devices and Intended Use . . .
2.2.2 Optimum Radiochemical Characteristics . . . . . . . . .
&.2 .3 Optimum In Viuo Distribution . . . . . . . . . . . . . . . . . . .
2.3 esirable Characteristics of Therapeutic Radiophar-
maceutical Drug Products . . . . . . . . . . . . . . . . . . . - . . . .
2.3.1 Optimum Radionuclide Characteristics Relative to
De.s ire.d Micro- and Macro-Radiation Dose Dis-
tnbution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.2 Optimum Radiochemical Characteristics . . . . . . . . . .
2.3.3 Optimum In Viuo Distribution Behavior . . . . . . . . . .
2.4 Factors Influencing Localization of Labeled Mate-
rials in Tiesues . . . . . . . . . . . . . . . . . . . . . . . . . . -. . . . . - . . .
2.4.1 General Kinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.2 Discussion of Factors Influencing Distribution . . . . .
2.4.3 Specific Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5 The Nature of Radionuclides Produced in Reactors
and Charged-Particle Accelerators . . . . . . . . . . . . . . . .
2.6 Acceptance Criteria for Radiopharmaceutical Drug
Products .............................. .... ......
2.6.1 Radionuclide Identity, Quantity and Purity . . . . . . .
2.6.2 Radiochemical Identity and Purity . . . . . . . . . . . . . . .
vi / CONTENTS
2.6.3 Content and Toxicity of Non-Radioactive Constitu-
ents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.4 In Vivo Distribution Behavior ...................
2.6.5 General Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.6 Sterility and Apyrogenicity .....................
2.6.7 Absorbed Radiation Dose . . . . . . . . . . . . . . . . . . . . . .
2.7 Regulations Regarding Production, Testing, Ship-
ping, and Utilization of Radiopharmaceutical Drug
Products for Human Use ..........................
2.8 Choice of Radiopharmaceutical Drug Product for a
Given Diagnostic Procedure or Treatment .........
2.9 Management of Misadministration of Radiopharma-
ceutical Drug Products . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.9.1 Administrative Responsibilities . . . . . . . . . . . . . . . . .
2.9.2 Medical Care Responsibilities ....................
.
3 Factors in Choosing an Instrument for Nuclear Medicine
Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1 General .........................................
3.2 Measurement Systems Used in Nuclear Medicine . .
3.2.1 Survey Instruments . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.2 Dose Calibrators ..............................
3.2.3 Sample Counters . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.4 h b eS ystems ................................
8.3 Imaging Syeteme Ueed in Nuclear Medicine
. . . . . .
3.3.1 Rectilinear Scannexs . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.2 Scintillation Cameras ...........................
3.3.3 Tomographic Imaging Systems . . . . . . . . . . . . . . .
3.3.4 X-Ray Fluorescence Imaging Systems ............
3.4 Properties of Radiation Detectors for Measurement
and Imaging Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.1 General .......................................
3.4.2 Sensitivity .....................................
3.4.3 Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5 Properties of Recording Devices Used in Nuclear
Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
3.5.1 Count and Count Rate Recording Techniques .....
3.5.2 Image Recording Techniques ....................
3.6 Resolution Factors Affecting the Choice of Systems
3.6.1 Temporal Factors .............................
3.6.2 Spatial Factors .................................
3.6.3 Energy Factors .................................
.
4 Radiation Dose ........................................
4.1 Radiation Dose from Administered Radionuclides
CONTENTS vii
4.1.1 General .......................................
4.1.2 Dose Rate From Internal Emitters ...............
4.1.3 Absorbed Radiation Dose Calculations . . . . . . . . . .
4.2 Effects of Internally Administered Radionuclides in
Man .............................................
4.2.1 Sources of Information ..........................
4.2.2 Review of Accidental and Unusual Occupational
Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.3 Medical Uses-Therapy .........................
4.2.4 Medica 4 Uses-Diagnosis ........................
4.2.5 Summary of Findings from Historical Review .....
4.2.6 Topics of Special Interest in Nuclear Medicine ....
5. Evalua. t.i on of Radionuclide Procedures and Their Clini-
cal Ut~llty. ............................................
5.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2 Evaluating the Role of New Nuclear Medical
Procedures .....: ..................................
5.2.1 A Priori Measures (of systems) and Figures of Merit
for Imaging Procedures .........................
5.2.2 Evaluation of Non-Imaging Procedures . . . . . . . . .
5.2.3 Evaluation of Therapy Procedures ...............
5.2.4 A Posteriori Measures ..........................
5.3 Measuring the Clinical Efficacy of Nuclear Medicine
Procedures ........................................
5.3.1 Nuclear Medicine Test Provides New Information .
5.3.2 Introduction of a Test lmproves Diagnostic
Accuracy .....................................
5.3.3 Introduction of a Test Leads to a Reduction in
Morbidity .....................................
5.3.4 Survival not Affected by Introduction of Nuclear
Medicine Test ..................................
5.4 Financial Costs and Cost Effectiveness ............
. 5.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6 Guidelines for Performing Nuclear Medicine Pro-
cedures .............................................
6.1 Basic Principles ...................................
6.2 Categories of Subjects .............................
6.2.1 Patients Receiving Radionuclides for Diagnostic
Purposes ......................................
6.2.2 Volunteer Subjects Receiving Radionuclides for In-
vestigative Purposes ...........................
6.3 Methods of Patient Dose Reduction ................
6.3.1 Routine Practices .............................
viii CONTENTS
6.3.2 Misadministrations ...................... . ..... 99
6.4 Radiation Protection Guides ....................... 99
6.5 Recommendations ................................. 101
6.5.1 General Recommendation ....................... 101
6.5.2 Thyroid Uptake of Iodine in Children ............ 101
6.5.3 Radionuclides in Women in Reproductive Years ... 102
6.5.4 Use of New Agents ............................. 102
APPENDIX A-Guidelines for the Clinical Evaluation of
Radiopharmaceutical Drugs .............................. 103
APPENDIX B-Radiation Absorbed Dose Estimates ..... 116
References ...............................................1 35
The NCRP ................................................ 151
NCRP Publications ........................................ 158
Index .....................................................1 69
1. Decision Making in Nuclc:~r
Medicine
1.1 Introduction
The practice of nuclear medicine necessitates informed rlecision
making in choosing the proper radionuclide, labeled compor~ud,; ~trd
instrumentation to be used in making a diagnosis or selecting the
proper therapeutic radionuclide and dose. Practitioners of this branch
of medicine must decide whether or not to perform a radioisotope
procedure on a given patient, which radioisotope studies are indicated,
and which are either not indicated or are contraindicated. Introduction
of new radiopharmaceutical drug products (RDPs) and new indications
for use of existing RDPs require decisions concerning the propriety of
their proposed use. Such decisions are made by governmental regula-
tory bodies, institutional review committees, nuclear medical personnel
performing routine clinical evaluations, clinical investigators, and fi-
nally, patients or experimental subjects themselves. Such decision
making is most objective when it is based on the best data available at
the time, which must be weighed and analyzed objectively.
While a number of source books are available that summarize
present-day practice of nuclear medicine, there is a need for an
information source organized around decision-making aspects for this
discipline. The present report is directed toward this need. It is
intended for use by all individuals and groups engaged in the decision-
making processes in nuclear medicine including, but not limited to,
personnel in government regulatory agencies, institutional committees
overseeing the clinical use of radioactive agents both for routine and
investigative purposes, and personnel in nuclear medicine laboratories
concerned with acquisition and use of equipment and RDPs for routine
and experimental purposes. It should also be of use to individuals who
wish to familiarize themselves with the nuclear medicine decision-
making process.
This document does not provide guidance on the space, facility, and
equipment requirements of a nuclear medicine laboratory, nor does it
address itself to the personnel requirements and the training required
to staff the laboratory. Neither is it concerned with the use of proce-
2 / 1. DECISION MAKING IN NUCLEAR MEDICINE
dures for safeguarding personnel and patients from hazards arising
from storage, preparation, administration, utilization, and evaluation
of radioactive materials, although familiarity with such information is
a prerequisite for use with decision-making procedures in nuclear
medicine. The reader should familiarize himself with these aspects of
the discipline; such information will be found in general reference texts
and in the following NCRP Reports whose titles indicate their con-
tents.
NCRP No. 30-Safe Handling of Radioactive Materials (1964)
NCRP No. 37-Precautions in the Management of Patients Who
Have Received Therapeutic Amounts of Radionu-
clides (1970)
NCRP No. 39-Basic Radiation Protection Criteria (1971)
NCRP No. 43-Review of the Current State of Radiation Protection
Philosophy (1975)
NCRP No. 48-Radiation Protection for Medical and Allied Health
Personnel (1976)
NCRP No. 57-Instrumentation and Monitoring Methods for Ra-
diation Protection (1978)
NCRP No. 58-A Handbook of Radioactivity Measurements Pro-
cedures ( 1978)
NCRP No. 59-Operational Radiation Safety Program (1978)
NCRP No. 65-Management of Persons Accidentally Contaminated
with Radionuclides (1980)
In addition to these sources, a World Health Organization report
provides guidance on facilities and personnel required in performing
nuclear medical procedures (WHO, 1976). The International Commis-
sion on Radiation Units and Measurements has published Report 32
Methods of Assessment of Absorbed Dose in Clinical Use of Radio-
nuclides (ICRU, 1979) which deals with the methods of evaluation of
absorbed dose received by the tissues of persons to whom radioactive
drug products have been administered. The Bureau of Radiological
Health has produced a document containing information regarding the
many recommendations and requirements for safe operation of a
nuclear medicine laboratory (HHS, 1982).
