Radiolabeled Monoclonal Antibodies for Imaging and Therapy

876 Pages·1988·15.46 MB·English

by  Peter D. Gorevic (auth.)

Radiolabeled Monoclonal
Antibodies for Imaging
and Therapy
NATO ASI Series
Advanced Science Institutes Series
A series presenting the results of activities sponsored by the NATO Science Committee,
which aims at the dissemination of advanced scientific and technological knowledge,
with a view to strengthening links between scientific communities.
The series is published by an international board of publishers in conjunction with the
NATO Scientific Affairs Division
A Life Sciences Plenum Publishing Corporation
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c
Mathematical Kluwer Academic Publishers
and Physical Sciences Dordrecht, Boston, and London
D Behavioral and Social Sciences
E Applied Sciences
F Computer and Systems Sciences Springer-Verlag
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H Cell Biology Paris, and Tokyo
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Volume 152-Radiolabeled Monoclonal Antibodies for Imaging and Therapy
edited by Suresh C. Srivastava
Series A: Life Sciences
Radiolabeled Monoclonal
Antibodies for Imaging
and Therapy
Edited by
Suresh C. Srivastava
Brookhaven National Laboratory
Upton, New York
Springer Science+Business Media, LLC
Proceedings of the NATO Advanced Study Institute on
Radiolabeled Monoclonal Antibodies for Imaging and Therapy:
Potential, Problems, and Prospects,
held July 20-August 1, 1986,
in Castelvecchio Pascali, Italy
Library of Congress Cataloging in Publication Data
NATO Advanced Study Institute on Radiolabeled Monoclonal Antibodies for
Imaging and Therapy: Potential, Problems, and Propects (1986: Castelvecchio
Pascali, Italy)
Radiolabeled monoclonal antibodies for imaging and therapy I edited by
Suresh C. Srivastava.
p. cm.-(NATO ASI series. Series A, Life sciences; v. 152)
"Proceedings of the NATO Advanced Study Institute on Radiolabeled
Monoclonal Antibodies for Imaging and Therapy: Potential, Problems, and Pros
pects, held July 20-Aug. 1, 1986 in Castelvecchio Pascali, Italy"-T.p. verso.
"Published in cooperation with NATO Scientific Affairs Division."
Includes bibliographies and indexes.
ISBN 978-1-4684-5540-3 ISBN 978-1-4684-5538-0 (eBook)
DOI 10.1007/978-1-4684-5538-0
1. Antibodies, Monoclonal-Therapeutic use-Congresses. 2. Antibodies,
Monoclonal-Diagnostic use-Congresses. 3. Cancer-Diagnosis-Congress
es. 4. Cancer-Radiotherapy-Congresses. 5. Radioimmunoimaging-Con
gresses. 6. Radloimmunotherapy-Congresses. 7. Tumors-Imaging-Con
gresses. I. Srivastava, Suresh C. II. North Atlantic Treaty Organization. Scientific
Affairs Division. Ill. Title. IV. Series.
[DNLM: 1. Antibodies, Monoclonal-congresses. 2. Diagnosis, Radioisotope
congresses. 3. Isotope Labeling-congresses. 4. Neoplasms radionuclide imag
ing-congresses. 5. Neoplasms therapy-congresses. QZ 266 N279r]
RC271.M65N37 1986
616.07'57-dc19
DNLM/DLC 88-19623
for Library of Congress CIP
© 1988 Springer Science+Business Media New York
Originally published by Plenum Press New York in 1988
Softcover reprint of the hardcover 1st edition 1988
All rights reserved
No part of this book may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means, electronic, mechanical, photocopying,
microfilming, recording, or otherwise, without written permission from the Publisher
PREFACE AND INTRODUCTION
The advent of hybridoma technology leading to the successful produc
tion of monoclonal antibodies against a variety of tumor-associated
antigens has, during the last decade, provided a very powerful tool for
research and clinical investigations. These highly specific reagents have
essentially replaced the polysera of the earlier days. The successful
demonstration of the many wide ranging capabilities of the monoclonal
antibody technique has already begun to exert an enormous impact on
diverse areas of research in basic science and medicine.
In particular, the potential of monoclonal antibodies to serve as
carriers for selective targeting of radionuclides to tumors for diagnosis
or therapy, has stimulated an intense surge of research interest and even
revived hopes of realizing Ehrlich's concept of the "magic bullet".
Indeed, the technology appears to be on the threshold of a revolution in
diagnosing and treating malignant disease. Much work remains to be done,
however, and even though the progress has been impressive, results to date
have shown only moderate success. There is no question that the limited
success we have achieved thus far is merely a prelude to the many more
exciting developments yet to come.
Although a number of meetings and specialized symposia of an average
duration of two to three days have addressed the subject of radiolabeled
monoclonal antibodies, an in-depth coverage has been lacking. The unique
format of the NATO Advanced Study Institutes was thought to be an effec
tive means to bring together experts from many relevant disciplines for
detailed scientific discussions and interactions, for generating new
ideas, and for promoting goals for future research in this area.
In response to this expectation, the present NATO ASI on "Radiolabeled
Monoclonal Antibodies for Imaging and Therapy: Potential, Problems, and
Prospects", was held in Castelvecchio Pascoli, Italy, during July 20-
August 1, 1986. The program was designed to provide the participants with
the broad perspective that is essential to gain insight into the most
important topics in this area of investigation. Review lectures as well
as focused scientific presentations describing the latest research data
were included. A number of workshops and short oral and poster presenta~
tions were interspersed throughout the program for maximum effectiveness.
Sessions were organized to address not only the advances in the field but
also to thoroughly analyze the implications, opportunities, and problems
associated with these advances.
This book is derived from the lectures and papers presented at this
meeting. The material has been divided into nine parts and grouped
together in a fashion so as to provide a logical progression into the
various aspects of labeled monoclonal antibody research. The review
papers by experts are intended to provide the necessary background and to
stimulate ideas for future developments.
v
The book starts with a general section on monoclonal antibody produc
tion, selection, and characterization, proceeds to a discussion of the
selection criteria and the production of radionuclides, includes sections
on radiolabeling techniques, immunoreactivity considerations, and in-vivo
pharmacokinetics, deals with discussions of dosimetry and imaging strate
gies, provides results of clinical studies on immunoimaging and immuno
therapy, and concludes with a section on cell labeling and thrombus
imaging applications. While every effort was made to group related topics
together, some overlaps could not be avoided. It is hoped that this
arrangement will effectively carry the reader through some of the basic
concepts to actual in-vitro and in-vivo experimental investigations, a
discussion of problems and concerns, and finally to representative clini
cal data in patients.
The submitted manuscripts were reviewed, edited, and occasionally
reorganized to maintain a reasonable uniformity in the style of presenta
tion. Extensive rewriting was necessary in a few cases; however, the
editor has endeavored not to change the substance or the emphasis of these
manuscripts inasmuch as possible.
The discussions following each presentation have been included since
it was felt that these not only amplified the authors' presentations with
views of the participants, but also greatly aided in sorting out a number
of workable hypotheses and solutions. Three workshops, starting first
with presentations by a panel of experts and then followed by audience
participation and discussion, are also included. The topics were as
follows: "Methods for Determining Immunoreactivity of Labeled Monoclonal
Antibodies - Problems and Pitfalls", "Radiobiological and Dosimetric
Considerations for Immunotherapy with Labeled Antibodies", and "Human
Anti-Mouse Antibody Response in Patients". The transcribing, editing (and
deciphering) of this seemingly endless taped material turned out to be a
mammoth undertaking and a constant challenge to everybody's patience. The
effort was, however, deemed worthwhile and it is the editor's hope that
the inclusion of this material will prove to be of substantial interest
and benefit to the reader.
Considerable effort was expended in rev1s1ng, correcting and proof
reading the manuscripts. Despite this, some typographical and syntax
errors may have remained. The editor accepts the final responsibility,
asks the readers' understanding, and hopes that the minor remaining errors
will not be too distracting.
While no claims are made for a text-book character for this volume, it
is sincerely believed that this book would prove to be a valuable refer
ence resource for those considering initiation of research in the area of
radiolabeled monoclonal antibodies as well as for the established investi
gators in the field. The results, the data, and the discussions included
in this volume will hopefully generate new ideas and contribute towards
paving the way for future research in this relatively new and exciting
area of investigation.
Upton, New York
December 1, 1987 Suresh C. Srivastava
vi
ACKNOWLEDGEMENTS
The primary sponsorship of this AS! by the North Atlantic Treaty
Organization, and the advice and cooperation of Dr. C. Sinclair of the
Scientific Affairs Division, are gratefully acknowledged. Thanks are due
to the United States Department of Energy, Office of Health and Environ
mental Research, who provided the much needed additional sponsorship.
The organization of the AS! and the preparation of this book have
required considerable help from many other sources. The management of
Brookhaven National Laboratory is to be thanked for their continued coope
ration and encouragement. I owe my special gratitude to the Co-directors,
Drs. R.C. Reba and J.-F. Chatal, as well as to the members of the Interna
tional Advisory Committee consisting of Drs. D. A. Goodwin, A.A. Epenetos,
J.-P. Mach, and P. Paras for their valuable help throughout this endeavor.
This AS! could not have been the success that it was without help from
the faculty and the lecturers, who despite their busy schedules accepted
my invitation to participate, shared their knowledge and expertise, and
made themselves available for discussions and interactions during the two
week period. I am deeply appreciative of their valuable contributions.
The participants ultimately deserve the credit for the scientifically
stimulating and socially enjoyable atmosphere that prevailed throughout
the meeting and for lending to the meeting a truly international flavor.
I am grateful to our many industrial friends, who generously provided
additional financial support. They are as follows:
~Abbott Laboratories, USA Dow Chemical Company, USA
Bristol-Meyers Company, USA Medi-Physics, Inc., USA
Capintec, Inc., USA Organon Teknika, NV, Belgium
Compagnie ORIS Industrie, France Siemens Gammasonics, Inc., USA
Cytogen Corporation, USA Sorin Biomedica, Italy
The management and the staff of the Il Ciocco International Center,
Castelvecchio Pascoli, Italy, and in particular Mr. Bruno Giannasi,
deserve thanks on behalf of the participants for their warm hospitality
and for providing excellent meeting facilities. I also take this oppor
tunity to acknowledge the considerable assistance I received from my
secretary, Ms Rae Bailey, from Ms Susan Kearney (conference secretary),
and from Ms Patricia Vann and her editorial staff at Plenum Publishing
Corporation, during various stages of manuscript preparation.
Last but not least, I owe a great debt to my family, especially to my
wife Maria, who so willingly gave up her various more interesting pursuits
and instead offered untiring help during the entire organizational
vii
process, attended to numerous administrative chores, and provided crucial
assistance during all phases of the preparation of this book.
Upton, New York Suresh C. Srivastava
December 1, 1987
viii
CONTENTS
PART I. General: Monoclonal Antibody Production,
Selection, and Characterization ......................... 1- 146
Immunochemistry of Hybridomas ................................... . 3
Peter D. Gorevic
Characterization and Selection Criteria of Monoclonal
Antibodies for Tumor Imaging Studies ..................... . 23
A. A. Noujaim, B. M. Longenecker, M. R. Suresh,
C. J. Turner, T. R. Sykes and G. D. MacLean
Tumor Markers and Their Relevance in the Design of
Radioirnmunoimaging Experiments ........................... . 39
A. A. Noujaim, B. M. Longenecker, M. R. Suresh,
G. D. MacLean, C. J. Turner and T. R. Sykes
Selection of Monoclonal Antibodies with Optimal Biological
Functions for Clinical Application ....................... . 51
John Powe, Michael Lubeck and Zenon Steplewski
Selection and Utilization of Monoclonal Antibody Defined
Melanoma Associated Antigens for Irnmunoscintigraphy
in Patients with Melanoma ................................ . 55
S. Ferrone, M. Temponi, D. Gargiulo, G. A.
Scassellati, R. Cavaliere, and P. G. Natali
Development and Characterization of Human Monoclonal
Antibodies and Their Application in the
Radioimmunodetection of Colon Carcinoma .................. . 75
Richard P. McCabe, Leona C. Peters, Martin V. Haspel,
Nicholas Pomato, and Jorge A. Carrasquillo
Progress in Diagnostic Immunoscintigraphy and First
Approach to Radioimmunotherapy of Colon Carcinoma ........ . 95
Jean-Pierre Mach, Franz Buchegger, Angelika Bischof
Delaloye, Sven Curchod, Ariane Studer, Pelham Douglas,
Serge Leyvraz, Jean-Philippe Gr8b, Francois Mosimann,
Jean-Claude Givel, Jacques Pettavel, and Bernard Delaloye
The Design of a Radiolabeled Monoclonal Antibody for
Radioimmunodiagnosis and Radioimmunotherapy................ 111
S. J. DeNardo, G. L. DeNardo, S. V. Deshpande,
G. P. Adams, D. J. Macey, S. L. Mills, A. L.
Epstein, and C. F. Meares
Immunohistochemistry and Correlation with Plasma Levels
of CA 19-9 and CEA in Gastrointestinal Tumors............. 123
M. Lorenz, R. P. Baum, G. Herrmann, R. Inglis,
and M. Schulz
Optimization of Mouse IgG Fragmentation Technique in the Selection
of Monoclonal Antibodies for Myocardial Infarct Imaging... 129
Catherine Larue, Corinne Chateigner, Patrick Gautier,
Jacques Planchenault and Jocelyne Leger
Sensitivity and Efficacy Indices for Oncologic Data Reporting.... 139
Alexander Gottschalk, Eugene Cornelius, and Paul B. Hoffer
PART II. Selection Criteria for Imaging and Therapy and
the Production of Radionuclides ........................ 147-192
Production and Use of Prospective Radionuc1ides for
Radioimmunotherapy........................................ 149
Leonard F. Hausner, Rita F. Straub, and
Suresh C. Srivastava
Criteria for the Selection of Nuclides for Radioimmunotherapy... 165
S. James Adelstein and Amin I. Kassis
Experience with Iodine-123 Labeled Antibodies.................... 177
Keith Britton and Marie Granowska
PART III. Radiohalogenation and Radiometal Labeling of
Monoclonal Antibodies................................. 193-268
Radiohalogenation of Antibodies: Chemical Aspects .............. . 195
Michael R. Zalutsky
Radiohalogenation of Monoclonal Antibodies: Experiences
with Radioiodination of Monoclonal Antibodies for
Radioimmunotherapy........................................ 215
James C. Reynolds, Patrick Maloney, Mark Rotman,
Richard Fejka, Raymond A. Farkas, Kunihiko Yokoyama,
and Steven M. Larson
Use of Bifunctional Chelating Agents for Radiolabeling
Antibodies................................................ 229
Claude F. Meares
Monoclonal Antibody Labeling with Indium-111 and Gadolinium
via DTPA Chelation on Selective and Nonselective
Sites of the Antibody..................................... 239
J. C. Saccavini, C. Curtet, J. Bohy, and C. Tellier
X