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Radiopharmaceuticals
AGuide toPET/CT and PET/MRI
FerdinandoCalabria
OrazioSchillaci
Editors
3rded.
123

Radiopharmaceuticals

Ferdinando Calabria • Orazio Schillaci
Editors
Radiopharmaceuticals
A Guide toPET/CT andPET/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, specically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms 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 specic 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 afliations.
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
18
F-uciclovine, to new intriguing applications of radiolabeled FAPI and
18
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 neuroinammation 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
18
F-FAZA.
vii

viii
https://t.me/med1917
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 FerdinandoCalabria
Rome, Italy OrazioSchillaci
Preface

Contents
https://t.me/med1917
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:
223
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
https://t.me/med1917
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

18
https://t.me/med1917
F-FDG
FerdinandoCalabria, AndreaCimini,
AntonioBagnato, DomenicoGullà,
GiuseppeL.Cascini, NicolettaUrbano,
andOrazioSchillaci
1
Abbreviations
18
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
18
F-Fluoro-deoxyglucose
computed tomography
SPECT/CT Single photon emission computed
tomography/computed tomography
SUVmax Maximum standardized uptake value
1.1 Synthesis
18
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 triate 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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