Handbook of Radiopharmaceuticals E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1493

Veröffentlichungsjahr: 2021

Beschreibung

The thoroughly updated new edition of the authoritative reference in Radiopharmaceutical Sciences The second edition of Handbook of Radiopharmaceuticals is a comprehensive review of the field, presenting up-to-date coverage of central topics such as radionuclide production, synthetic methodology, radiopharmaceutical development and regulations, and a wide range of practical applications. A valuable reference work for those new to the Radiopharmaceutical Sciences and experienced professionals alike, this volume explores the latest concepts and issues involving both targeted diagnostic and therapeutic radiopharmaceuticals. Contributions from a team of experts from across sub-disciplines provide readers with an immersive examination of radiochemistry, nuclear medicine, molecular imaging, and more. Since the first edition of the Handbook was published, Nuclear Medicine and Radiopharmaceutical Sciences have undergone major changes. New radiopharmaceuticals for diagnosis and therapy have been approved by the FDA, the number of clinical PET and SPECT scans have increased significantly, and advances in Artificial Intelligence have dramatically improved research techniques. This fully revised edition reflects the current state of the field and features substantially updated and expanded content. New chapters cover topics including current Good Manufacturing Practice (cGMP), regulatory oversight, novel approaches to quality control--ensuring that readers are informed of the exciting developments of recent years. This important resource: * Features extensive new and revised content throughout * Covers key areas of application for diagnosis and therapy in oncology, neurology, and cardiology * Emphasizes the multidisciplinary nature of Radiopharmaceutical Sciences * Discusses how drug companies are using modern radiopharmaceutical imaging techniques to support drug discovery * Examines current and emerging applications of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) Edited by recognized experts in radiochemistry and PET imaging, Handbook of Radiopharmaceuticals: Radiochemistry and Applications, 2 nd Edition is an indispensable reference for post-doctoral fellows, research scientists, and professionals in the pharmaceutical industry, and for academics, graduate students, and newcomers in the field of radiopharmaceuticals.

Leseprobe

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 first published 2021

© 2021 John Wiley & Sons Ltd.

Edition History

John Wiley & Sons, Ltd. (1e, 2003)

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Michael R. Kilbourn and Peter J.H. Scott to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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Library of Congress Cataloging‐in‐Publication Data

Names: Kilbourn, Michael R., editor. | Scott, Peter J. H., editor.

Title: Handbook of radiopharmaceuticals : methodology and applications /

   edited by Michael R. Kilbourn, University 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.

Identifiers: LCCN 2020025975 (print) | LCCN 2020025976 (ebook) | ISBN

   9781119500544 (cloth) | ISBN 9781119500551 (adobe pdf) | ISBN

   9781119500568 (epub)

Subjects: LCSH: Radiopharmaceuticals–Handbooks, manuals, etc.

Classification: LCC RS431.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: Wiley

Cover Image: Radio logical image of human body organs, Creative Commons

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 expanding the PET Cyclotron and Radiochemistry program, where he pursued research efforts 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 Interdepartmental 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.

List of Contributors

Franklin I. Aigbirhio

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences

University of Cambridge, Cambridge Biomedical Campus

Cambridge, UK

Stephen J. Archibald

Positron Emission Tomography Research Centre, Department of Biomedical Sciences, Faculty of Health Sciences

University of Hull

Hull, UK

Nicolaas I. Bohnen

Department of Radiology

University of Michigan

Ann Arbor, MI, US

Department of Neurology

University of Michigan

Ann Arbor, MI, USA

Neurology Service and GRECC

VAAAHS

Ann Arbor, MI, USA

John P. Bois

Department of Cardiovascular Diseases

Mayo Clinic

Rochester, MN, USA

Guy Bormans

Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences

University of Leuven

Leuven, Belgium

Allen F. Brooks

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Laura Bruton

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Benjamin P. Burke

Positron Emission Tomography Research Centre, Department of Biomedical Sciences, Faculty of Health Sciences

University of Hull

Hull, UK

Elizabeth R. Butch

Department of Diagnostic Imaging

St. Jude Children's Research Hospital

Memphis, TN, USA

Dae Yoon Chi

Department of Chemistry

Sogang University

Seoul

Korea

Mara Clark

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Frederik Cleeren

Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences

University of Leuven

Leuven,

Belgium

David W. Dick

Department of Radiology

University of Iowa

Iowa City, IA, USA

Mehdi Djekidel

Nuclear Medicine and Molecular Imaging

Sidra Medicine

Qatar

David J. Donnelly

Bristol‐Myers Squibb Pharmaceutical Research and Development

Princeton, NJ, USA

Arkadij Elizarov

Trace‐Ability

Los Angeles, California

USA

Vanessa Gómez‐Vallejo

Radiochemistry and Nuclear Imaging Group

CIC biomaGUNE

San Sebastián,

Spain

Jeroen A.C.M. Goos

Department of Radiology

Memorial Sloan‐Kettering Cancer Center

New York, NY, USA

Robert J. Gropler

Mallinckrodt Institute of Radiology

Washington University School of Medicine,

St Louis, MO, USA

Jason P. Holland

Department of Chemistry

University of Zurich

Zurich,

Switzerland

Salma Jivan

,

Helen Wills Neuroscience Institute, University of California

Berkley, CA, USA

Steven Kealey

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences

University of Cambridge

Cambridge Biomedical Campus

Cambridge, UK

Outi Keinänen

Department of Chemistry, Hunter College

The City University of New York

New York, NY, USA

Michael R. Kilbourn

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Suzanne E. Lapi

Department of Radiology

University of Alabama at Birmingham

Birmingham, AL, USA;

Department of Chemistry

University of Alabama at Birmingham

Birmingham, AL, USA

Jason S. Lewis

,

Department of Radiology

Memorial Sloan‐Kettering Cancer Center

Birmingham, AL, USA;

Molecular Pharmacology Program and the Radiochemistry and Molecular Imaging Probes Core

Memorial Sloan Kettering Cancer Center

Birmingham, AL, USA;

Departments of Radiology and Pharmacology

Weill Cornell Medical College

New York, NY, USA

Jordi Llop

Radiochemistry and Nuclear Imaging Group

CIC biomaGUNE

San Sebastián

Spain

Fernando López‐Gallego

Heterogeneous Biocatalysis Laboratory

Instituto de Síntesis Química y Catálisis Homogénea (ISQCH‐CSIC), University of Zaragoza

Zaragoza

Spain;

ARAID, Aragon I+D foundation

Zaragoza

Spain

C. Shaun Loveless

Department of Radiology

University of Alabama at Birmingham

Birmingham, AL, USA;

Department of Chemistry

Washington University in St. Louis

St Louis, MO, USA

Robert H. Mach

Department of Radiology, Perelman School of Medicine

University of Pennsylvania

Philadelphia, PA, USA

Katarina J. Makaravage

Department of Chemistry

University of Michigan

Ann Arbor, MI, USA

Dionysia Papagiannopoulou

Department of Pharmaceutical Chemistry, School of Pharmacy

Aristotle University of Thessaloniki

Thessaloniki

Greece

Krishna R. Pulagam

Radiochemistry and Nuclear Imaging Group

CIC biomaGUNE

San Sebastián

Spain

Sean W. Reilly

Department of Radiology, Perelman School of Medicine

University of Pennsylvania

Philadelphia, PA, USA

Luka Rejc

Radiochemistry and Nuclear Imaging Group

CIC biomaGUNE

San Sebastián

Spain;

Faculty of Chemistry and Chemical Technology,

University of Ljubljana

Ljubljana

Slovenia

Melissa E. Rodnick

,

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Thomas J. Ruth

TRIUMF and BC Cancer Research Centre

Vancouver, British Columbia,

Canada

Melanie S. Sanford

Department of Chemistry

University of Michigan

Ann Arbor, MI, USA

Peter J.H. Scott

Department of Radiology

University of Michigan

Ann Arbor, Michigan

USA

Selena M. Sephton

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences

University of Cambridge

Cambridge Biomedical Campus

Cambridge, UK

Barry L. Shulkin

Department of Diagnostic Imaging

St. Jude Children's Research Hospital

Memphis, TN, USA

Scott E. Snyder

Department of Diagnostic Imaging

St. Jude Children's Research Hospital

Memphis, TN, USA

Alexandra R. Sowa Dumond

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Stephen Thompson

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences

University of Cambridge

Cambridge Biomedical Campus

Cambridge, UK

Alfons Verbruggen

Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences

University of Leuven

Leuven, Belgium

Koen Vermeulen

Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences

University of Leuven

Leuven, Belgium

Jay Wright

Department of Radiology

University of Michigan

Ann Arbor, MI, USA

Brian M. Zeglis

Department of Radiology

Memorial Sloan‐Kettering Cancer Center

New York, NY, USA;

Department of Chemistry, Hunter College

The City University of New York

New York, NY, USA;

PhD program in chemistry

Graduate Center of the City University of New York,

New York, NY, USA;

Departments of Radiology and Pharmacology

Weill Cornell Medical College

New York, NY, USA

Foreword

When Mike Welch and Carol Redvanly edited the first edition of the Handbook of Radiopharmaceuticals in 2003, the field of radiopharmaceutical sciences was undergoing a number of important changes. [18F]Fludeoxyglucose ([18F]FDG) had been recently approved by the US Food and Drug Administration (FDA), and reimbursement coverage was in place from the US Centers for Medicare and Medicaid Services. This was creating a burgeoning market for commercial production and distribution of [18F]FDG, which in turn drove innovation in both radiopharmaceutical manufacture and clinical scanner technology. At the same time, increasing numbers of radiochemistry facilities were stimulating the development of many different radiopharmaceuticals for research applications.

This innovation and research have continued over the intervening years, and as we complete this new edition at the start of the Roaring Twenties, we have been reflecting that it is another exciting and transformative time in the fields of nuclear medicine and radiopharmaceutical sciences! New radiopharmaceuticals continue to be approved by the FDA, including PET radiotracers for brain and cancer imaging and theranostics for cancer treatment. These radiopharmaceuticals are transforming the lives of the patients we diagnose and treat in our clinicals every day. Coupled with lobbying efforts by the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and others to inform reimbursement policy, significant efforts by industrial partners to develop the radiochemistry and PET imaging suites of the future, initiatives by academic colleagues to standardize the nomenclature of our science,1 and the expected impact of artificial intelligence on our discipline, nuclear medicine has been invigorated and is transforming from a research technique into a powerful standard of care.

This growth in nuclear medicine is apparent in day‐to‐day operations around the world. In an established market like the United States, over 1.5 million clinical PET scans currently occur, and yet we have been impressed to see the number of clinical PET scans taking place at the University of Michigan double between 2014 and 2019. There is also substantial growth occurring in developing markets, and at the 2019 International Symposium of Radiopharmaceutical Sciences (ISRS) that took place in Beijing, it was remarked that a new PET scanner is being installed in China every two weeks! The concomitant growth in the use of radiotherapeutics means that innovation in the radiopharmaceutical sciences to meet these new demands is as important today as when the first edition of the Handbook was published.

We were both attracted to the fields of nuclear medicine and radiopharmaceutical sciences early in our careers for a number of reasons. First, radiopharmaceutical sciences is an exciting application of basic science with immediate impact on patient care; second, the translational aspect of the research is appealing; and finally, we thoroughly enjoy the diverse and multidisciplinary nature of the work. Our field exists at the intersection of medicine, biology, chemistry, physics, and engineering, and, with the exception of Antarctica, research applications and clinical uses of nuclear medicine are occurring on every continent.

The articles in the new edition of the Handbook demonstrate that the field of radiopharmaceutical sciences remains as multidisciplinary as ever. We have tried to keep this new edition faithful to the format of the original and asked authors to provide knowledge updates in their various sub‐disciplines (radionuclide production, radiochemistry, applications of radiopharmaceuticals) that have occurred since the first edition was published. However, the evolution of the radiopharmaceutical sciences since that time, particularly in regards to current Good Manufacturing Practice (cGMP), regulatory oversight, and novel approaches to quality control, have necessitated the addition of new chapters in these areas.

We look forward to how our field continues to develop in the next 20 years, as we witness new technology and applications in the radiopharmaceutical sciences that might find their way into a future edition of the Handbook and continue the legacy of Mike Welch and the other visionaries who started our field.

Michael R. Kilbourn

Peter J.H. Scott

June 2020

Ann Arbor MI, USA

Note

1

See Coenen et al.,

Nucl Med Biol

. 2017;55:v‐xi, doi: 10.1016/j.nucmedbio.2017.09.004.

Preface

The first edition of the Handbook of Radiopharmaceuticals was published near the start of the twenty‐first century. Dedicated by Michael J. Welch and Carol Redvanly to the memory of Alfred P. Wolf, that volume provided students and researchers with a comprehensive review of the field of radiochemistry and its growing importance in medicine.

This second edition of the Handbook is dedicated to the memories of Michael Welch and the many other notable scientists and physicians that the field has lost in recent years, many of whom served as mentors or colleagues of the contributing authors to this edition. The radiochemical sciences and medical imaging have grown tremendously just in the past two decades, and as we enter the third decade of the twenty‐first century, there is the expectation that the future holds untold important and impactful advances. In this edition of the Handbook, we have emphasized chapters that bring the reader up to date on the exciting developments of recent years. We thank the editorial team at John Wiley & Sons as well as all of the authors, the majority of whom are new contributors, for their valuable time and effort in bringing this new edition of the Handbook to reality.

Michael R. Kilbourn

Peter J.H. Scott

June 2020

Ann Arbor MI, USA

Abbreviations

5‐HT1A

serotonin 1A receptor

ACh

acetylcholine

AChE

acetylcholinesterase

AcOH

acetic acid

ACPC

1‐aminocyclopentanecarboxylic acid

AD

Alzheimer’s disease

ADC

antibody drug conjugate

ADM

s‐adenosyl‐

L

‐methionine

AI

artificial intelligence

ALARA

as low as reasonably achievable

AMDP

aminomethylenediphosphonate

AMT

α‐Methyl‐

L

‐tryptophan

ATP

adenosine triphosphate

ATTR

amyloid transthyretin

BACE

beta‐secretase

BAT

brown adipose tissue

BBB

blood‐brain barrier

B

max

maximum concentration of target binding sites

BOx

benzoxazole

BP

binding potential

BP

British Pharmacopeia

Bq

becquerel

BTA

aryl‐benzothiazole

BZD

benzodiazepine

CAD

coronary artery disease

cAMP

cyclic adenosine monophosphate

CBF

cerebral blood flow

CBS

compton backscattered

[

11

C]ACHC

aminocyclohexanecarboxylic acid

[

11

C]DASB

[

11

C]3‐amino‐4‐(2‐dimethylaminomethylphenylsulfanyl)‐benzonitrile

[

11

C]DOPA

[

11

C dihydroxyphenylalanine

[

11

C]DTBZ

[

11

C]Dihydrotetrabenazine

[

11

C]HED

[

11

C]hydroxyephedrine

[

11

C]PiB

[

11

C]Pittsburgh compound B (PIB ([N‐methyl‐

11

C]6‐Me‐BTA‐1)

CFR

Code of Federal Regulations

cGMP

current Good Manufacturing Practice

Ci

curie

ClogD

calculated distribution coefficient at pH 7.4

ClogP

calculated partition coefficient

CMC

chemistry, manufacturing, and controls

CMO

contract manufacturing organization

CNS

central nervous system

COMT

catecholamine O‐methyl transferase

CSF

cerebrospinal fluid

CT

computed tomography

CTA

clinical trial application

CV

cardiovascular

CXCR4

CXC‐chemokine receptor‐4

Da

daltons

DAT

dopamine transporter

DBU

1,8‐diazabicyclo[5.4.0]undec‐7‐ene

DDD

drug discovery and development

DIPE

di‐isopropyl ether

DMA

N,N

‐dimethylacetamide

DMF

N,N

‐dimethylformamide

DMF

drug master file

DMSO

dimethyl sulfoxide

DNA

deoxyribose nucleic acid

DOTA

1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid

DPA

dipicolylamine

DPzA

dipyrazolylamine

Dx

dextran

EANM

European Association of Nuclear Medicine

EC

electron capture

ECD

[

99m

Tc]ethylcysteine dimer

eCTD

electronic common technical document

EGFR

epidermal growth factor receptor

eLINACS

electron linear accelerators

EMA

European Medicines Agency

EOB

end‐of‐bombardment

EOS

end‐of‐synthesis

EP

European Pharmacopeia

EPI

epinephrine

EtOH

ethanol

EU

European Union

eV

electron volt

FA

fatty acid

FAAH

fatty acid amide hydrolase

[

18

F]FACBC

1‐amino‐3‐[

18

F]fluorocyclobutanecarboxylic acid (Fluciclovine, Axumin)

FDA

Food and Drug Administration

[

18

F]FDG

2‐deoxy‐2‐[

18

F]fluoro‐D‐glucose

FDH

formate dehydrogenase

[

18

F]FDOPA

6‐[

18

F]fluorodihydroxyphenylalanine

[

18

F]FES

[

18

F]fluoroestradiol

[

18

F]FET

2‐[

18

F]fluoroethyl)‐L‐tyrosine

[

18

F]FMISO

[

18

F]fluoromisonidazole

[

18

F]FMT

[

18

F]fluoromethyltyrosine

[

18

F]FPEB

[

18

F]3‐fluoro‐5‐(pyridin‐2‐ ylethynyl)benzonitrile

[

18

F]FSPG

(S‐4‐(3‐[

18

F]fluoropropyl)‐L‐glutamic acid

g

gram

GABA

gamma amino butyric acid

GC

gas chromatography

GIST

gastrointestinal stromal tumors

GLP

Good Laboratory Practice

GMP

Good Manufacturing Practice

HBED

N,N’

‐bis(2‐hydroxybenzyl)ethylendiamine‐

N,N’

‐diacetic acid

HDA

hexadecanoic acid

HER

human epidermal growth factor receptor

HEU

highly enriched uranium

HITS

high‐throughput screening

HIV/AIDS

human immunodeficiency virus/ acquired immunodeficiency syndrome

HMPAO

[

99m

Tc]hexamethylpropyleneamine oxime

HMR

heart mediastinal ratio

HPLC

high‐performance liquid chromatography

HSA

human serum albumin

HYNIC

hydrazinonicotinamide

IAEA

International Atomic Energy Agency

IB

investigators brochure

IBZM

iodobenzamide

ICH

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use

ID

injected dose

ID/g

injected dose per gram

IHC

immunohistochemistry

IMPD

investigational medicinal product dossier

IMZ

iomazenil

IND

investigational new drug

iNOS

inducible nitric oxide synthase

IVS

interventricular septum

K

d

equilibrium dissociation constant, affinity of ligand toward the target

LAF

laminar air flow

LET

linear energy transfer

LV

left ventricular

MAA

macroaggregated albumin

mAb

monoclonal antibody

MAO

monoamine oxidase

MCA

multi‐channel analyzer

MCNPX

Monte Carlo N‐Particle eXtended

MCP‐1

monocyte chemoattractant protein‐1

mCRPC

metastatic castration resistant prostate cancer

MDP

methylenediphosphonate

MeV

mega electron volt

MIBG

meta‐iodobenzylguanidine

Min

minutes

mmol

millimoles

MMP

matrix metalloproteinases

μmol

micromoles

MPI

myocardial perfusion imaging

MPI

myocardial perfusion reserve

MPTP

1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine

MRI

magnetic resonance imaging

MR2

muscarinic receptor 2

NA

natural abundance

NDA

new drug application

NE

norepinephrine

NET

neuroendocrine tumors

NK‐1

neurokinin‐1 receptor

nM

nanomolar

NOS

nitric oxide synthase

NOTA

1,4,7‐triazacyclononane‐triacetic acid

NPH

normal pressure hydrocephalus

NPs

nanoparticles

OCT

organic cation transporter

PBR

peripheral benzodiazepine receptor

PC

prostate cancer

PD

pharmacodynamics

PD‐L1

program death ligand 1 receptor

PET

positron emission tomography

Pgp

p‐glycoprotein

PHEN

phenylephrine

p.i.

post‐injection

PiB

Pittsburgh Compound B

PIDA

phenyliodonium diacetate

PK

pharmacokinetics

pKa

acid dissociation constant

PRRT

peptide receptor radionuclide therapy

PSMA

prostate‐specific membrane antigen

PTFE

polytetrafluoroethane

QA

quality assurance

QC

quality control

QMA

quaternary methyl ammonium

QNB

quiniclidinyl benzilate

R&D

research and development

RBA

relative binding affinity

RCY

radiochemical yield

RDRC

Radioactive Drug Research Committee

RGD

arginine‐glycine‐aspartic acid

RIT

radioimmunotherapy

RLD

reference listed drug

RLT

radioligand therapy

RV

right ventricular

SERT

serotonin transporter

S

N

Ar

nucleophilic aromatic substitution

SPE

solid phase extraction

SPECT

single photon emission computed tomography

SSRIs

selective serotonin reuptake inhibitors

SSTR‐2

somatostatin receptor 2

SUV

standardized uptake value

TACN

triazamacrocycle 1,4,7‐triazacyclononane

TAT

targeted alpha therapy

TATE

(Tyr

3

‐Thr

6

)‐octreotide

TBA

tetrabutylammonium

TBAF

tetra‐

n

‐butylammonium fluoride

TCEP

tris(2‐carboxyethyl)phosphine

Tf

triflate

THF

tetrahydrofuran

TNBC

triple‐negative breast cancer

TOC

(Tyr

3

)‐octreotide

TSPO

translocator protein, 18 kDa

TTR

transthyretin

USP

United States Pharmacopeia

UV

ultraviolet

VA

ventriculo‐atrial

VAChT

vesicular transporter for acetylcholine

VMAT2

vesicular monoamine transporter type 2

VP

ventriculo‐peritoneal

WHO

World Health Organization