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Radiopharmaceuticals
AGuide toPET/CT and PET/MRI
FerdinandoCalabria OrazioSchillaci
Editors
3rded.
123
Ferdinando Calabria • Orazio Schillaci
Editors
Radiopharmaceuticals
A Guide toPET/CT andPET/MRI
3rd ed. 2024
Editors
Ferdinando Calabria Department of Nuclear Medicine and Theranostics Mariano Santo Hospital Cosenza, Italy
Orazio Schillaci Department of Biomedicine and Prevention University of Rome Tor Vergata Rome, Italy
ISBN 978-3-031-54195-7 ISBN 978-3-031-54196-4 (eBook)
https://doi.org/10.1007/978-3-031-54196-4
predecessor edition: Radiopharmaceuticals Ed:2, English, 2020.
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2020, 2024 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
If disposing of this product, please recycle the paper.
The dedication by Orazio Schillaci:
https://t.me/med1917
To Nicoletta, Maria Beatrice, and Agnese Felicia. The dedication by Ferdinando Calabria: To Rosario, my father.
Preface
https://t.me/med1917
Three years have passed since the publication of the previous edition, and we humbly must express our gratitude to the readers who have chosen this book as a resource for their learning process. This newly revised book aims to pro­vide readers with an accessible, usable, and concise atlas guide to PET molecular imaging. Additionally, we appreciate the compliments from our peers. Conversely, we have the urge to add to its content in order to keep it useful in the broad eld of PET molecular imaging.
Nuclear medicine is a discipline intrinsically based on the properties of these biological molecules; therefore, with the precious help of many Italian and European colleagues, the current edition of the book is expanded to cover further important chapters, from the imaging of prostate cancer with
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F-uciclovine, to new intriguing applications of radiolabeled FAPI and
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F-uoroestradiol, a further amino acid tracer as the 18F-uorothymidine, and the 68Ga-Pentixafor, the tracer for imaging the chemokine receptor involved in tumor growth.
Some old chapters have been updated, in particular, due to the recent applications of radiolabeled choline, 18F-DOPA, 68Ga-PSMA, and 18F-NaF; other chapters are kept in the new edition, for the peculiarities of, in primis, the 18F-FDG and, consequently, 11C-methionine, somatostatin receptor ana­logs, 18F-FET, 64Cu-radiopharmaceuticals, amyloid tracers, 82Rb,
223
Ra-dichloride, and τ tracers. It is noteworthy to state that some of these diagnostic tracers represent the essential step in theranostics, while other agents enlarged the eld of applications of PET to neurology and cardiology. Moreover, two additional chapters concern neuroinammation imaging with TSPO agents and the hypoxia pathway with
This book now includes 30 PET radiopharmaceuticals, with more than 250 clinical cases demonstrating their diagnostic characteristics. Because it is yet unknown what the perfect radiopharmaceutical in nuclear medicine would be, the authors also discuss physiological variations in distribution and diag­nostic problems related to particular biochemical pathways.
As in the past version, the authors describe the molecular pathway, biodis­tribution, physiopathology, and kinetics of each radiopharmaceutical, as the basis of the diagnostic role. The essential diagnostic features and the most common clinical indications are discussed for each tracer. Therefore, in this new version of the book, nuclear physicians, radiologists, and young col­leagues will also nd a friendly guide to the interpretation of PET images with the most important diagnostic tracers actually in use. Once again, we
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F-FAZA.
vii
viii
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know that this is a provisional list of PET tracers; at the same time, we are pleased about this because it represents the mirror image of the vitality of our discipline.
The goal of the work is still to assist professionals in their approach to a certain topic. In our opinion, the key for young nuclear physicians in under­standing the landscape of PET imaging should be this synthesis between the data offered by clinicians and researchers and the reader’s point of view. This synthesis should be taken into account in its truest sense: from the ancient Greek σύvθεσις (súnthesis), which is the result of “putting together” some­thing coherent and comprehensive by combining simpler things. Because of the ongoing process of innovation, a scientist cannot claim to know every­thing; instead, they must strive to know as much as they can. For this purpose, we sincerely thank colleagues, researchers, and scientists who helped us to write the book, particularly in collecting clinical cases, describing diagnostic molecules, and synthesizing a large amount of data to provide the reader with a quick guide to PET molecular imaging.
Cosenza, Italy FerdinandoCalabria Rome, Italy OrazioSchillaci
Preface
Contents
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1 18F-FDG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Ferdinando Calabria, Andrea Cimini, Antonio Bagnato, Domenico Gullà, Giuseppe L. Cascini, Nicoletta Urbano, and Orazio Schillaci
2 18F-DOPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Ferdinando Calabria, Mario Leporace, and Orazio Schillaci
3 The Lipogenesis Pathway: Radiolabeled Choline . . . . . . . . . . . . 59
Ferdinando Calabria, Mario Leporace, Marzia Colandrea, Giuseppe L. Cascini, and Orazio Schillaci
4 18F-FET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Giorgio Treglia and Barbara Muoio
5 18F-NaF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Ferdinando Calabria, Mario Leporace, Antonio Bagnato, and Orazio Schillaci
6 Somatostatin Receptor Analogs (68Ga-DOTATOC,
68
Ga-DOTANOC, 68Ga-DOTATATE) . . . . . . . . . . . . . . . . . . . . . . . 105
Luca Filippi, Patrizia Pizzichini, Oreste Bagni, and Francesco Scopinaro
7 64Cu-Radiopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Ferdinando Calabria, Antonio Bagnato, Vincenzo Gangemi, Rosina Paonessa, Mario Leporace, Nicoletta Urbano, and Giuseppe Lucio Cascini
8 Amyloid Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Agostino Chiaravalloti, Ferdinando Calabria, Antonio Bagnato, and Orazio Schillaci
9 PET Myocardial Perfusion Imaging: 82Rb . . . . . . . . . . . . . . . . . . 151
Maria Luisa De Rimini and Giovanni Borrelli
10 The Bone Pathway:
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Ra-Dichloride . . . . . . . . . . . . . . . . . . . . . . 187
Laura Evangelista and Alessandra Zorz
11 11C-Methionine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Sebastiano Cosentino, Fabrizio Scopelliti, Gabriella Murè, Sara Baldari, and Massimo Ippolito
ix
x
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12 68Ga-PSMA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Robert Pichler, Johannes Wolfsgruber, Ferdinando Calabria, Orazio Schillaci, and Andreas Dunzinger
13 PET Biomarkers for Tau Pathology . . . . . . . . . . . . . . . . . . . . . . . 235
Antoine Leuzy, Kerstin Heurling, and Michael Schöll
14 18F-Fluciclovine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Riccardo Pirisino, Oreste Bagni, Orazio Schillaci, and Luca Filippi
15 Radiolabeled FAPI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Andrea Cimini, Maria Ricci, Laura Travascio, Habibollah Dadgar, Hossein Arabi, Fabio Cusella, Nasim Norouzbeigi, Habib Zaidi, and Batool Albalooshi
16 18F-FES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Maria Rosaria Ruggiero, Roberta Visentin, and Salvatore Annunziata
17 68Ga-Pentixafor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Francesca Russo, Massimo Menichini, Maria Ricci, Laura Travascio, Habibollah Dadgar, Hossein Arabi, Nasim Norouzbeigi, Maria Silvia De Feo, Habib Zaidi, Batool Albalooshi, and Andrea Cimini
Contents
18 18F-Thymidine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Laura Travascio, Federico Padovano, Marzia Colandrea, Mario Leporace, Luca Frontino, Bhagwant Rai Mittal, Ferdinando Calabria, and Rakhee Vatsa
19 Imaging Biomarkers of Neuroinflammations:
TSPO Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Annachiara Arnone and Pierpaolo Alongi
20 Hypoxia Pathway: 18F-FAZA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Pierpaolo Alongi, Paola Mapelli, Viola Vultaggio, Annachiara Arnone, and Maria Picchio
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https://t.me/med1917
F-FDG
FerdinandoCalabria, AndreaCimini, AntonioBagnato, DomenicoGullà, GiuseppeL.Cascini, NicolettaUrbano, andOrazioSchillaci
1
Abbreviations
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F-FDG BOLD Blood oxygenation level dependent FLAIR Fluid attenuation inversion recovery MIP Maximum intensity projection MRI Magnetic resonance imaging PET/CT Positron emission tomography/
ROI Region of interest
F. Calabria (*) · A. Bagnato Department of Nuclear Medicine and Theranostics, Mariano Santo Hospital, Cosenza, Italy
A. Cimini Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, University Hospital Tor Vergata, Rome, Italy
D. Gullà Neuroimaging PET/MRI Research Unit, Institute of Molecular Bioimaging and Physiology, Italian National Research Council, IBFM-CNR, Catanzaro, Italy
G. L. Cascini Nuclear Medicine Unit, Department of Diagnostic Imaging, Magna Graecia University, Catanzaro, Italy
N. Urbano Nuclear Medicine Unit, University Hospital “Tor Vergata”, Rome, Italy
O. Schillaci Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
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F-Fluoro-deoxyglucose
computed tomography
SPECT/CT Single photon emission computed
tomography/computed tomography
SUVmax Maximum standardized uptake value
1.1 Synthesis
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F-FDG is a glucose analog with the hydroxyl group on the 2-carbon of a glucose molecule replaced by 18F, a β+ emitter isotope of uorine.
18
F-FDG can be synthesized by either electro­philic or nucleophilic uorination reactions. The rst synthesis of 18F-FDG was obtained in 1976 by electrophilic uorination [1]. Instead, the chemical reaction of nucleophilic substitution involves the addition of a nucleophilic molecule (a negatively charged molecule) into a molecule with a leaving group (electron drawing group attached to the parent molecule through an unsta­ble chemical bond). Nucleophilic uorination, using mannose triate as precursor and tetrabu­tylammonium salts, is largely used because of the high yield and short reaction time [ quality control requirements of 18F-FDG regard the identity of radionuclide, radiochemical purity, pH, residual solvent, sterility, and the level of bacterial endotoxin. These tests should be n­ished after the tracer can be released [2].
2]. The main
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 F. Calabria, O. Schillaci (eds.), Radiopharmaceuticals,
https://doi.org/10.1007/978-3-031-54196-4_1
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