Table Of ContentAnimal Models in Radiotracer Design
Animal Models in
Radiotracer Design
Edited by
RICHARD M. LAMBRECHT
WILLIAM C. ECKELMAN
With 57 Figures
Springer-Verlag
New York Berlin Heidelberg Tokyo
Richard M. Lambrecht William C. Eckelman
Chemistry Department Section of Radiopharmaceutical
Brookhaven National Laboratory Chemistry
Upton, NY 11973, USA George Washington University
Medical Center
Washington. DC 20037, USA
Library of Congress Cataloging in Publication Data
Main entry under title:
Animal models in radiotracer design.
Includes bibliographical references and index.
I. Radioisotopes-Therapeutic use. 2. Radioisotopes
in medical diagnosis. 3. Animal models in research.
I. Lambrecht, Richard M .. 1943- II. Eckelman, William C. [DNLM: 1.
Radioisotopes-Diagnostic use-Congresses. 2. Drug screening-Methods
Congresses. 3. Models. Biological-Congresses, WN 445 A598 1982]
RM849.A54 1983 615.8'424'0724 83-10553
© 1983 by Springer-Verlag New York Inc.
Softcover reprint of the hardcover 1st edition 1983
All rights reserved. No part of this book may be translated or reproduced in any fonn without
written permission from Springer-Verlag. 175 Fifth Avenue, New York, New York 10010,
U.S.A.
The use of general descriptive names, trade names, trademarks, etc., in this publication, even
if the former are not especially idcntified. is not to be taken as a sign that such names, as
understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely
by anyone.
Typeset by BiComp, Incorporated. York. Pennsylvania.
9 8 7 6 5 4 3 2
ISBN -13:978-1-4612-5598-7 e-ISBN -13 :978-1-4612-5596-3
DOl: 10.1007/978-1-4612-5596-3
Foreword
The editors have asked me to write this foreword probably for two reasons: First,
I have spent 35 years trying to develop radiolabeled compounds that would help
diagnose and treat disease. I, and the people from my laboratory, have been much
involved with developing Nan'I for the diagnosis and treatment of hyperthyroidism
and well-differentiated thyroid cancer. Second, I was a participant throughout the
entire symposium upon which this book is based.
Our latest '311-labeled compound, [l3lll metaiodobenzylguanidine, took us 13
years to develop. It has succeeded in diagnosing and treating adrenergic tumors
under circumstances where Na'311 would have failed for the diagnosis and treatment
of thyroid cancer. I therefore hope that more scientists will be attracted to this field.
This book is written by intelligent, experienced investigators who are knowl
edgeable. It is a must for anyone new in the field. For the experienced, I would
like to remind you that I attended the entire symposium; the breadth and timeliness
of the update has helped us to redirect some of our current efforts into more
scientifically productive channels.
William H. Beierwaltes, M.D.
Ann Arbor, July 1982
Preface
Radiotracers with potential applications in medical research and radiopharmaceu
ticals intended for use in clinical medicine are evaluated extensively in animals
prior to human use. The choice of the animal model plays a critical role in the
eventual success or failure of the animal studies in predicting in vivo selectivity of
a radiotracer for a physiologic process, the biodistribution, and the pharmacokinetics
in man. This book is a first attempt at gathering information on the effect of choice
of animal species on the development of radiopharmaceuticals and radiotracers for
biomedical research. Our intent was to produce a resource guide for both newcomers
and experts in the radiopharmaceutical sciences. Chemists, physicians, pharmacists,
cellular biologists, veterinarians, and technologists will find this first comprehensive
compilation to be both informative and timely.
The publication of this book is the result of two successful workshops sponsored
by the Radiopharmaceutical Science Council of the Society of Nuclear Medicine
held in conjunction with meetings of the Society in Phoenix in January and in
Miami Beach in June, 1982. Recognized experts were asked to identify, review,
and critically explore how existing animal models are being effectively used and
to evaluate examples of the successful and unsuccessful research with the models
described in the vast and rapidly expanding literature of radiotracer development.
The outstanding reception of the material presented in the lectures led to this book.
All manuscripts were reviewed by referees.
Acknowledgments
William C. Eckelman is supported at George Washington Medical Center by the
Department of Radiology and the following grants from the National Institutes of
Health: HL-19127, CA-18675, CA-28462; and the U.S. Department of Energy,
Contract No. ASO 5 82 ER 60039.
Richard M. Lambrecht acknowledges the continuing scientific collaborations and
professional advice of Alfred P. Wolf. He extends special thanks and appreciation
to Heidi Sylvestre for her encouragement and for being a friend. We gratefully
acknowledge Lois Caligiuri for secretarial assistance.
Research at Brookhaven National Laboratory in Radiopharmaceutical Chemistry
and Nuclear Medicine is supported by the U.S. Department of Energy and its Office
of Health and Environmental Research. Research is also supported in part by the
National Institute of Neurological and Communicative Disorders and Stroke.
William C. Eckelman
Richard M. Lambrecht
Upton, December 1982
Contents
ANIMAL MODELS IN BIOMEDICAL RESEARCH AND
RADIOTRACER DESIGN
Richard M. Lambrecht, William C. Eckelman, and Aldo Rescigno
Brief Survey of Chapters 15
Guidelines for Research with Animals 17
References 19
2 THE DEVELOPMENT OF RADIOTRACERS THAT ARE
SUBSTRATES FOR (CATECHOLAMINE) UPTAKE AND
1
UPTAKE
2
Edward A. Carr, Jr. 35
Introduction: Development of Informational Drugs 35
Catecholamine Uptaket and Uptakez 37
Compounds Other Than Catecholamines that Participate in Uptake) and
Uptake 44
2
Species Differences 50
The Special Case of the Adrenal Medulla 51
Other Extraneuronal Uptake 52
Possible Pathological Role of Changes in Uptake) 54
Possible Future Directions of Research 55
x Contents
Summary 56
References 57
3 MONOCLONAL ANTIBODIES: THE DESIGN OF
APPROPRIATE CARRIER AND EVALUATION SYSTEMS
Brian M. Gallagher 61
Introduction 61
Monoclonal Antibody Applications 66
Requirements for the Receptor Antigen 68
Requirements for the Carrier Antibody 70
Tumor Model Systems 78
Summary 97
References 99
4 SMALL ANIMAL ONCOLOGICAL MODELS FOR
SCREENING DIAGNOSTIC RADIOTRACERS
Leonard I. Wiebe 107
Introduction 107
The Need for Animal Tumor Models 108
Cancer 108
Classification of Neoplasms 109
Growth and Spread of Neoplasms 110
Animal Tumor Models 110
Selection of Animal Tumor Models Based on Mechanism of
Uptake of the Radiotracer 114
Animal Tumor Models in the Literature of Radiotracers and
Radiopharmaceuticals 115
References 136
5 lllln-LABELED PLATELETS FOR THE DETECTION OF
VASCULAR DISORDERS IN ANIMAL MODELS
Carla J. Mathias and Michael J. Welch 149
Introduction 149
Acute Arterial Lesion Model 155
Atherosclerosis 157
Coronary Artery Thrombosis 160
Vascular Grafts 162
References 164
Contents xi
6 ANIMAL MODELS IN THE STUDY OF HEPATOBILIARY
RADIOTRACERS
Alan R. Fritzberg and Duane C. Bloedow 179
Introduction and Characteristics of Hepatobiliary Agents 179
Species and Hepatobiliary Excretion 812
Laboratory Animal Technique Considerations 192
Summary 203
References 204
7 EXPERIMENTAL MODELS AND EVALUATION OF ANIMAL
DATA FOR RENAL RADIODIAGNOSTIC AGENTS
John C. McAfee and Gopal Subramanian 211
Introduction 211
Evaluation of Animal Biodistribution Data 211
Comparison of Biodistribution of Renal Agents in Different
Species 213
Choice of Animal Models 217
Models of Human Renal Diseases in the Rat 222
Conclusions 224
References 225
INDEX 229
Contributors
William H. Beierwaltes, Department of Internal Medicine, Division of Nuclear
Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Duane C. Bloedow, Department of Pharmacy, University of Colorado, Denver,
CO 80202, USA
Edward A. Carr, Jr., Department of Pharmacology and Therapeutics, State Uni
versity of New York and The Buffalo Veteran's Administration Medical Center,
Buffalo, NY 14214, USA
William C. Eckelman, Division of Nuclear Medicine, Radiopharmaceutical Chem
istry Section, George Washington University Medical Center, Washington,
DC 20037, USA
Alan R. Fritzberg, Department of Pharmacy, University of Utah, Salt Lake City,
UT 84112, USA
Brian M. Gallagher, Division of Pharmacology and Animal Studies, New England
Nuclear Corporation, North Billerica, MA 01845, USA
Richard M. Lambrecht, Chemistry Department, Brookhaven National Laboratory,
Upton, NY 11973, USA
Carla J. Mathias, Division of Radiation Sciences, The Edward Mallinckrodt Institute
of Radiology, Washington University, St. Louis, MO 63110, USA
John G. McAfee, Department of Nuclear Medicine and Radiological Sciences, State
University of New York, Upstate Medical Center, Syracuse, NY 13210, USA
