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HANDBOOK OF RADIOPHARMACEUTICALS:
METHODOLOGY
ANDAPPLICATIONS
HANDBOOK OF RADIOPHARMACEUTICALS
METHODOLOGY AND APPLICATIONS
Second Edition
MICHAEL R. KILBOURN
University of Michigan Ann Arbor, USA
PETER J.H. SCOTT
University of Michigan Ann Arbor, USA
 
This second edition rst published 2021 © 2021 John Wiley & Sons Ltd .
Edition History
John Wiley & Sons, Ltd. (1e, 2003)
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The right of Michael R. Kilbourn and Peter J.H. Scott to be identied as the auth ors of the editorial material in this work has been asserted in accordance with law.
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In view of ongoing research, equipment modications, changes in governmental regulations , and the const ant ow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of us age and for added warnings and precautions. While the publisher and authors have used their best eorts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the content s of this work and specically discl aim all warranties, including without limitation any implied warranties of merchantability or tness for a particul ar purpose. No warranty may b e created or extended by sales representatives, written sales materials or promotional statement s for this work . The fact that an organization, website, or product is referred to in this work as a citation and/ or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the under standing that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Fur ther, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of prot or any other commercial damages, including but not limited to special , incidental, consequential, or other damages.
Library of Congress Cataloging-in-Publication Data
Names : Kilbourn, Michael R., editor. | Scott, Peter J. H., editor. Title: Handbook of radiopharmaceutical s : methodology and applications / edited by Michael R. Kilbourn, Universit y of Michigan and Peter J.H . Scott, University of Michigan. Description: Second edition. | Hoboken, NJ : Wiley, 2021. | Revised edition of: Handbook of radiopharmaceuticals : radiochemistry and applications / editors, Michael J. Welch, Carol S. Redvanly. c2003. | Includes bibliographical references and index. Identier s: LCCN 2020025975 (print) | LCCN 2020025976 (ebook) | IS BN 9781119500544 (cloth) | ISBN 9781119500551 (adobe pdf) | ISBN 9781119500568 (epub) Subjects: LCSH : Radiophar maceuticals– Handbooks, manual s, etc. Classication: LCC RS 431.R34 H36 2021 (print) | LCC RS431.R34 (ebook) | DDC 615.8/42– dc23 LC record available at https://lccn.loc.gov/2020025975 LC ebook record available at https://lccn.loc.gov/2020025976
Cover Design: W iley Cover Image: Radio logical image of human body organs, Creative Commons
Set in 9/13pt Ubuntu by SPi Global , Chennai, India
10 9 8 7 6 5 4 3 2 1

Contents

About the Editors vii List of Contributors ix
Foreword xv Preface xvii Abbreviations xix
PART I: Introduction to Radiopharmaceuticals 1
Chapter 1: Targeted Diagnostic Radiopharmaceuticals: Design
Options forSmall-Molecule
Radiotracers 3
Michael R. Kilbourn
Chapter 2: Concepts andIssues forTherapeutic Radiopharmaceuticals 23
Alexandra R. Sowa Dumond and
Peter J.H. Scott
PART II: Production of Radionuclides 43
Chapter 3: Production of Short Half-Life PET Radionuclides 45
Michael R. Kilbourn, Melissa E. Rodnick
and Mara Clark
Chapter 4: Production of Radionuclides Used in SPECT 71
Salma Jivan and Thomas J. Ruth
Chapter 5: Production ofTherapeutic Radionuclides 89
C. Shaun Loveless and Suzanne E. Lapi
PART III: Synthetic Methods for Radiopharmaceuticals 107
Chapter 6: Synthesis of 13N-
15
and
Radiopharmaceuticals 109
Krishna R. Pulagam, Vanessa
Gómez-Vallejo, Fernando López-Gallego,
Luka Rejc and Jordi Llop
Chapter 7: Radiochemistry withCarbon-11 143
Stephen Thompson, Steven Kealey,
Selena Milicevic Sephton and
Franklin I. Aigbirhio
Chapter 8: Fluorine-18 Radiochemistry 251
Allen F. Brooks, Katarina J. Makaravage,
Jay Wright, Melanie S. Sanford and
Peter J. H. Scott
Chapter 9: Labeling with Gallium-68 291
Benjamin P. Burke and Stephen
J. Archibald
Chapter 10: Cu-Mediated
Radiohalogenation of
Organoboranes 325
Sean W. Reilly and Robert H. Mach
Chapter 11: The Radiochemistry ofZirconium 343
Jason P. Holland
O-Labeled
V
Chapter 12:
99m
Tc
Radiopharmaceutical Chemistry 375
Dionysia Papagiannopoulou
PART IV: Practical Aspects of Radiopharmaceutical Production and Use 435
PART V: Major Applications of Radiopharmaceuticals 533
Chapter 18: Radiopharmaceuticals inOncology 535
Jeroen A.C.M. Goos, Outi Keinänen,
Brian M. Zeglis, and Jason S. Lewis
Chapter 13: Automated
Synthesis Modules for PET Radiochemistry 437
Laura Bruton and Peter J.H. Scott
Chapter 14: Automation of PET Radiopharmaceutical Quality Control 457
Arkadij Mikhailovich Elizarov
Chapter 15: Moving PET Drugs from the Lab to the Patient in the USA 491
David W. Dick
Chapter 16: Moving from the Lab to the Patient in Asia 501
Dae Yoon Chi
Chapter 17: Moving a Radiotracer from Bench to Bedside
in Europe 515
Koen Vermeulen, Alfons Verbruggen,
Guy Bormans and Frederik Cleeren
Chapter 19: Neurological Applications of
Radiopharmaceuticals 571
Mehdi Djekidel and Nicolaas I. Bohnen
Chapter 20: Cardiac Applications of
Radiopharmaceuticals 607
John P. Bois and Robert J. Gropler
Chapter 21: Radiopharmaceuticals
inPediatric Nuclear Medicine 653
Scott E. Snyder, Elizabeth R. Butch and
Barry L. Shulkin
Chapter 22: PET Imaging in Drug Discovery and Development 703
David J. Donnelly, Ph.D
Index 727
VI Contents
About theEditors
Michael R. Kilbourn is an emeritus professor of radiology at the University of Michigan
Medical School. He retired from the university after 25 years of directing and expand-
ing the PET Cyclotron and Radiochemistry program, where he pursued research eorts
directed at the design, development, and application of novel PET radiotracers for Par­kinson’s and Alzheimer’s diseases.
Peter J.H. Scott is an associate professor of radiology and a member of the Interde-
partmental Program in Medicinal Chemistry at the University of Michigan. He is director of the University of Michigan Positron Emission Tomography (PET) Center and runs a research group developing new radiochemistry methodology and novel PET radio­tracers. His laboratory is funded by the US Department of Energy, the National Insti­tutes of Health, and the Alzheimer’s Association and has multiple collaborations with academic institutions and biotech and pharmaceutical companies all over the world. Professor Scott has edited four other books for Wiley, including two volumes of Radiochemical Syntheses.
vii