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- •Contents
- •List of Contributors
- •Foreword
- •Preface
- •Abbreviations
- •1.1 INTRODUCTION
- •1.7 SUMMARY
- •REFERENCES
- •2.1 INTRODUCTION
- •2.2 THERANOSTICS
- •REFERENCES
- •3.1 INTRODUCTION
- •3.3 68Ge/68Ga GENERATORS
- •REFERENCES
- •4.1 INTRODUCTION
- •4.2 TECHNETIUM-99m
- •4.3 IODINE-131
- •4.4 XENON-133
- •4.5 CYCLOTRON-PRODUCED RADIONUCLIDES
- •4.6 THALLIUM-201
- •4.7 GALLIUM-67
- •4.8 INDIUM-111
- •4.9 IODINE-123
- •4.A. APPENDIX
- •REFERENCES
- •5.1 INTRODUCTION
- •5.7 SUMMARY
- •7.1 INTRODUCTION
- •REFERENCES
- •8.1 INTRODUCTION
- •9.1 INTRODUCTION
- •10.2 Cu-MEDIATED RADIOFLUORINATION
- •10.3 Cu-MEDIATED HEAVY HALIDE RADIOHALOGENATION
- •10.4 CONCLUSIONS
- •REFERENCES
- •11.1 INTRODUCTION
- •REFERENCES
- •12.1 INTRODUCTION
- •12.3 MYOCARDIAL IMAGING AGENTS
- •12.5 BRAIN IMAGING AGENTS
- •12.6 RENAL IMAGING AGENTS
- •12.7 BONE IMAGING AGENTS
- •12.9 SENTINEL LYMPH NODE IMAGING AGENTS
- •12.12 CONCLUDING REMARKS
- •13.1 INTRODUCTION
- •13.2 EARLY RADIOCHEMISTRY SYNTHESIS MODULES
- •13.3 MODERN CASSETTE-BASED MODULES
- •13.5 HYBRID MODULES
- •13.6 MICROFLUIDIC SYSTEMS
- •13.8 AUTOMATED QUALITY CONTROL TESTING
- •REFERENCES
- •14.1 OVERVIEW
- •14.4 DRIVERS OF AUTOMATED QC
- •14.5 BARRIERS TO QC AUTOMATION
- •14.6 QC INNOVATION



HANDBOOK OF
RADIOPHARMACEUTICALS:
METHODOLOGY
ANDAPPLICATIONS


HANDBOOK OF
RADIOPHARMACEUTICALS
METHODOLOGY AND
APPLICATIONS
Second Edition
Edited by
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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how to obtain permission to reuse material from this title is available at http://w ww.wiley.com/go/permissions.
The right of Michael R. Kilbourn and Peter J.H. Scott to be identied as the auth ors of the editorial material in this work
has been asserted in accordance with law.
Registered Oces
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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.
Identier 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.
Classication: 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 forSmall-Molecule
Radiotracers 3
Michael R. Kilbourn
Chapter 2: Concepts
andIssues forTherapeutic
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
ofTherapeutic 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
withCarbon-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
ofZirconium 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
inOncology 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
inPediatric 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 theEditors
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 eorts
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

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