Articles

Development of a fluorine-18 radiolabelled fluorescent chalcone: evaluated for detecting glycogen

Glycogen is a multibranched polysaccharide of glucose produced by cells to store energy and plays a key role in cancer. A previously reported fluorescent probe (CDg4) was shown to selectively bind glycogen in ...

Authors: Louis Allott, Diana Brickute, Cen Chen, Marta Braga, Chris Barnes, Ning Wang and Eric O. Aboagye

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

The use of radiolabelled antibodies was proposed in 1970s for staging of malignant tumours. Intensive research established chemistry for radiolabelling of proteins and understanding of factors determining biod...

Authors: Javad Garousi, Anna Orlova, Fredrik Y. Frejd and Vladimir Tolmachev

Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [⁶⁴Cu]copper PET/CT

Copper is essential for enzymatic processes throughout the body. [⁶⁴Cu]copper (⁶⁴Cu) positron emission tomography (PET) has been investigated as a diagnostic tool for certain malignancies, but has not yet been us...

Authors: Kristoffer Kjærgaard, Thomas Damgaard Sandahl, Kim Frisch, Karina Højrup Vase, Susanne Keiding, Hendrik Vilstrup, Peter Ott, Lars Christian Gormsen and Ole Lajord Munk

In vitro hypoxia responsiveness of [¹⁸F] FDG and [¹⁸F] FAZA retention: influence of shaking versus stagnant conditions, glass versus polystyrene substrata and cell number down-scaling

In vitro experiments using radiolabeled molecules is fundamental for Positron emission tomography (PET) or single photon emission computed tomography (SPECT) tracer development and various metabolic assays, bu...

Authors: Morten Busk, Michael R. Horsman, Jens Overgaard and Steen Jakobsen

Synthesis, in vitro and in vivo evaluation of ¹¹C-O-methylated arylpiperazines as potential serotonin 1A (5-HT_1A) receptor antagonist radiotracers

Serotonin 1A (5-HT_1A) receptors are implicated in the pathogenesis of several psychiatric and neurodegenerative disorders motivating the development of suitable radiotracers for in vivo positron emission tomograp...

Authors: Vidya Narayanaswami, Junchao Tong, Ferdinando Fiorino, Beatrice Severino, Rosa Sparaco, Elisa Magli, Flavia Giordano, Peter M. Bloomfield, Jaya Prabhakaran, J. John Mann, Neil Vasdev, Kenneth Dahl and J. S. Dileep Kumar

New sensitive method for HEPES quantification in ⁶⁸Ga-radiopharmaceuticals

The introduction of a GMP-certified ⁶⁸Ga-generator spurred the application of ⁶⁸Ga-radiopharmaceuticals. Several radiosynthesis of ⁶⁸Ga-radiopharmaceuticals are more efficient and robust when performed with 2-[4-...

Authors: I. F. Antunes, G. M. Franssen, R. Zijlma, P. Laverman, H. H. Boersma and P. H. Elsinga

Development, validation and regulatory acceptance of improved purification and simplified quality control of [¹³N] Ammonia

[¹³N]Ammonia is a cyclotron produced myocardial perfusion imaging agent. With the development of high-yielding [¹³N]ammonia cyclotron targets using a solution of 5 mM ethanol in water, there was a need to develop...

Authors: Daniel L. Yokell, Peter A. Rice, Ramesh Neelamegam and Georges El Fakhri

Automated synthesis and quality control of [^99mTc]Tc-PSMA for radioguided surgery (in a [⁶⁸Ga]Ga-PSMA workflow)

Lymph node dissection is a therapeutic option for prostate cancer patients with a high risk of- or proven lymph node metastases. Radioguided surgery after intravenous injection of [^99mTc]Tc-PSMA could improve the...

Authors: Else A. Aalbersberg, Lotte van Andel, Martine M. Geluk-Jonker, Jos H. Beijnen, Marcel P. M. Stokkel and Jeroen J. M. A. Hendrikx

Validation of a cost-effective alternative for a radiochromatography method to be used in a developing country

The radiochemical purity (RCP) of technetium-99m labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In low-income settings, it may not be possible to use compendial ...

Authors: F. P. Ekoume, H. H. Boersma, F. Dong à Zok and S. M. Rubow

Fully-automated production of [⁶⁸Ga]Ga-PentixaFor on the module Modular Lab-PharmTracer

PentixaFor is a promising radiopharmaceutical for positron emission tomography in the detection of different tumor entities and other diseases. Until now, the synthesis of [⁶⁸Ga]Ga-PentixaFor was reported for the...

Authors: Sarah Spreckelmeyer, Oliver Schulze and Winfried Brenner

EANM guideline on the validation of analytical methods for radiopharmaceuticals

To fulfil good manufacturing requirements, analytical methods for the analysis of pharmaceuticals for human and vetinary use must be validated. The International Conference on Harmonization of Technical Requir...

Authors: Nic Gillings, Sergio Todde, Martin Behe, Clemens Decristoforo, Philip Elsinga, Valentina Ferrari, Olaug Hjelstuen, Petra Kolenc Peitl, Jacek Koziorowski, Peter Laverman, Thomas L. Mindt, Meltem Ocak and Marianne Patt

What is the potential impact of the IsoDAR cyclotron on radioisotope production: a review

The IsoDAR collaboration is developing a high-current cyclotron for a neutrino search experiment. Designed to deliver 10 mA of 60 MeV protons, the current and power of this cyclotron far exceed those of existi...

Authors: Loyd H. Waites, Jose R. Alonso, Roger Barlow and Janet M. Conrad

Otto: a 4.04 GBq (109 mCi) ⁶⁸Ge/⁶⁸Ga generator, first of its kind - extended quality control and performance evaluation in the clinical production of [⁶⁸Ga]Ga-PSMA-11

Here we report on the comprehensive quality control of a 4.04 GBq (109 mCi) generator supplied by itG (Munich, Germany), and used for routine production of [⁶⁸Ga]Ga-PSMA-11 for clinical imaging. The performance o...

Authors: Nicole N. Waterhouse, Alejandro Amor-Coarasa, Anastasia Nikolopoulou and John W. Babich

Automated GMP compliant production of [¹⁸F]AlF-NOTA-octreotide

Gallium-68 labeled synthetic somatostatin analogs for PET/CT imaging are the current gold standard for somatostatin receptor imaging in neuroendocrine tumor patients. Despite good imaging properties, their use...

Authors: Térence Tshibangu, Christopher Cawthorne, Kim Serdons, Elin Pauwels, Willy Gsell, Guy Bormans, Christophe M. Deroose and Frederik Cleeren

Synthesis and validation of [¹⁸F]mBPET-1, a fluorine-18 labelled mTOR inhibitor derivative based on a benzofuran backbone

Targeted therapy of HER2 positive breast cancer has led to clinical success in some cases with primary and secondary resistance being major obstacles. Due to the substantial involvement of mTOR kinase in cell ...

Authors: Christian W. Wichmann, Yit Wooi Goh, Adam C. Parslow, Angela Rigopoulos, Nancy Guo, Andrew M. Scott, Uwe Ackermann and Jonathan M. White

Production of radiometals in liquid targets

Over the last several years, the use of radiometals has gained increasing relevance in supporting the continuous development of new, complementary and more specific biological targeting agents. Radiopharmaceut...

Authors: Sergio J. C. do Carmo, Peter J. H. Scott and Francisco Alves

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET)

Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), we demonstrate that simple micr...

Authors: Ksenia Lisova, Bao Ying Chen, Jia Wang, Kelly Mun-Ming Fong, Peter M. Clark and R. Michael van Dam

Pitfalls and solutions of the fully-automated radiosynthesis of [¹¹C]metoclopramide

[¹¹C]Metoclopramide is a new radiotracer for investigating the activity of P-glycoprotein at the blood-brain barrier. A highly stable and reproducible radiosynthesis is a prerequisite for clinical studies applyin...

Authors: Verena Pichler, Marius Ozenil, Karsten Bamminger, Chrysoula Vraka, Marcus Hacker, Oliver Langer and Wolfgang Wadsak

Improved synthesis of SV2A targeting radiotracer [¹¹C]UCB-J

[¹¹C]UCB-J is a tracer developed for PET (positron emission tomography) that has high affinity towards synaptic vesicle glycoprotein 2A (SV2A), a protein believed to participate in the regulation of neurotransmit...

Authors: Johanna Rokka, Eva Schlein and Jonas Eriksson

Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse...

Authors: Peter Wierstra, Gerwin Sandker, Erik Aarntzen, Martin Gotthardt, Gosse Adema, Johan Bussink, René Raavé and Sandra Heskamp

Fast and efficient copper-mediated ¹⁸F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying

Copper-mediated radiofluorination is a straightforward method to produce a variety of [¹⁸F]fluoroarenes and [¹⁸F]fluoroheteroarenes. To minimize the number of steps in the production of ¹⁸F-labelled radiopharmace...

Authors: Salla Orvokki Lahdenpohja, Noora Annika Rajala, Johan Rajander and Anna Kaarina Kirjavainen

Auger electrons for cancer therapy – a review

Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. ¹¹¹In, ⁶⁷Ga, ^99mTc, ^195mPt, ¹²⁵I and ¹²³I). This energy is deposited over nanometre-micro...

Authors: Anthony Ku, Valerie J. Facca, Zhongli Cai and Raymond M. Reilly

Ethanol effects on ⁶⁸Ga-radiolabelling efficacy and radiolysis in automated synthesis utilizing NaCl post-processing

Recent studies showed that ethanol in the reaction mixture improves radiolabelling with trivalent radiometals in terms of precursor amount, reaction time, reaction temperature and radiolysis. With regard to cl...

Authors: Michael Meisenheimer, Stefan Kürpig, Markus Essler and Elisabeth Eppard

[¹¹C]Carbon monoxide: advances in production and application to PET radiotracer development over the past 15 years

[¹¹C]Carbon monoxide is an appealing synthon for introducing carbon-11 at a carbonyl position (C=O) in a wide variety of chemotypes (e.g., amides, ketones, acids, esters, and ureas). The prevalence of the carbony...

Authors: Carlotta Taddei and Victor W. Pike

Development and implementation of ISAR, a new synthesis platform for radiopharmaceutical production

PET radiopharmaceutical development and the implementation of a production method on a synthesis module is a complex and time-intensive task since new synthesis methods must be adapted to the confines of the s...

Authors: Christopher Frank, Georg Winter, Fredrik Rensei, Victor Samper, Allen F. Brooks, Brian G. Hockley, Bradford D. Henderson, Christian Rensch and Peter J. H. Scott

Automated preparation of clinical grade [⁶⁸Ga]Ga-DOTA-CP04, a cholecystokinin-2 receptor agonist, using iPHASE MultiSyn synthesis platform

Gallium-68 ([⁶⁸Ga]Ga) labelled radiopharmaceuticals have become a valuable tool in clinical practice using Positron Emission Tomography (PET). These agents are typically produced on-site owing to the short half-l...

Authors: Mohammad B. Haskali, Peter D. Roselt, David Binns, Amit Hetsron, Stan Poniger, Craig A. Hutton and Rodney J. Hicks

Radionuclides: medicinal products or rather starting materials?

The EU directive 2001/83 describes the community code for medicinal products for human use including radiopharmaceuticals. In its current definition, also radionuclide precursors, such as fluorine-18, need to ...

Authors: Oliver Neels, Marianne Patt and Clemens Decristoforo

Evaluation of polydentate picolinic acid chelating ligands and an α-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-produced ²²⁵Ac

Actinium-225 (²²⁵Ac, t_1/2 = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered the development of a suitable Ac-chelating...

Authors: Caterina F. Ramogida, Andrew K. H. Robertson, Una Jermilova, Chengcheng Zhang, Hua Yang, Peter Kunz, Jens Lassen, Ivica Bratanovic, Victoria Brown, Lily Southcott, Cristina Rodríguez-Rodríguez, Valery Radchenko, François Bénard, Chris Orvig and Paul Schaffer

Improved synthesis of [¹⁸F] fallypride and characterization of a Huntington’s disease mouse model, zQ175DN KI, using longitudinal PET imaging of D2/D3 receptors

Dopamine receptors are involved in pathophysiology of neuropsychiatric diseases, including Huntington’s disease (HD). PET imaging of dopamine D2 receptors (D2R) in HD patients has demonstrated 40% decrease in ...

Authors: Tuulia Huhtala, Pekka Poutiainen, Jussi Rytkönen, Kimmo Lehtimäki, Teija Parkkari, Iiris Kasanen, Anu J. Airaksinen, Teija Koivula, Patrick Sweeney, Outi Kontkanen, John Wityak, Celia Dominiquez and Larry C. Park

The various therapeutic applications of the medical isotope holmium-166: a narrative review

Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which ca...

Authors: Nienke J. M. Klaassen, Mark J. Arntz, Alexandra Gil Arranja, Joey Roosen and J. Frank W. Nijsen

AAZTA⁵/AAZTA⁵-TOC: synthesis and radiochemical evaluation with ⁶⁸Ga, ⁴⁴Sc and ¹⁷⁷Lu

AAZTA (1,4-bis (carboxymethyl)-6-[bis (carboxymethyl)]amino-6-methylperhydro-1,4-diazepine) based chelators were initially developed in the context of magnetic resonance imaging. First radiochemical studies sh...

Authors: Jean-Philippe Sinnes, Johannes Nagel and Frank Rösch

Current radiotracers to image neurodegenerative diseases

The term of neurodegenerative diseases covers a heterogeneous group of disorders that are distinguished by progressive degeneration of the structure and function of the nervous system such as dementias, moveme...

Authors: Solveig Tiepolt, Marianne Patt, Gayane Aghakhanyan, Philipp M. Meyer, Swen Hesse, Henryk Barthel and Osama Sabri

Targeting of activated fibroblasts for imaging and therapy

Tumors form a complex environment consisting of a variety of non-malignant cells. Especially cancer-associated fibroblasts have been shown to have an important role for different aspects of malignant tumors su...

Authors: Thomas Lindner, Anastasia Loktev, Frederik Giesel, Clemens Kratochwil, Annette Altmann and Uwe Haberkorn

Clinical-grade N-(4-[¹⁸F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans

Molecular imaging of immune cells might be a potential tool for response prediction, treatment evaluation and patient selection in inflammatory diseases as well as oncology. Targeting interleukin-2 (IL2) recep...

Authors: Elly L. van der Veen, Inês F. Antunes, Petra Maarsingh, Janet Hessels-Scheper, Rolf Zijlma, Hendrikus H. Boersma, Annelies Jorritsma-Smit, Geke A. P. Hospers, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge and Erik F. J. de Vries

Fully-automated radiosynthesis of the amyloid tracer [¹¹C] PiB via direct [¹¹C]CO₂ fixation-reduction

The β-amyloid radiotracer [¹¹C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer’s Disease and related dementias. For clinical use, [¹¹C] PiB is produced using the ¹¹C-met...

Authors: Pablo Buccino, Eduardo Savio and Williams Porcal

Radionuclide generator-based production of therapeutic ¹⁷⁷Lu from its long-lived isomer ^177mLu

In this work, a lutetium-177 (¹⁷⁷Lu) production method based on the separation of nuclear isomers, ^177mLu & ¹⁷⁷Lu, is reported. The ^177mLu-¹⁷⁷Lu separation is performed by combining the use of DOTA & DOTA-labelle...

Authors: Rupali Bhardwaj, Hubert Th. Wolterbeek, Antonia G. Denkova and Pablo Serra-Crespo

Production and characterization of no-carrier-added ¹⁶¹Tb as an alternative to the clinically-applied ¹⁷⁷Lu for radionuclide therapy

¹⁶¹Tb is an interesting radionuclide for cancer treatment, showing similar decay characteristics and chemical behavior to clinically-employed ¹⁷⁷Lu. The therapeutic effect of ¹⁶¹Tb, however, may be enhanced due t...

Authors: Nadezda Gracheva, Cristina Müller, Zeynep Talip, Stephan Heinitz, Ulli Köster, Jan Rijn Zeevaart, Alexander Vögele, Roger Schibli and Nicholas P. van der Meulen

Have you looked for “stranger things” in your automated PET dose dispensing system? A process and operators qualification scheme

Many nuclear medicine departments have equipped themselves with automated dispensing systems (ADS) for PET radiopharmaceuticals, in both the operators’ and the patients’ interests. Whether partially or fully a...

Authors: Tristan Martin, Anaïs Moyon, Cyril Fersing, Evan Terrier, Aude Gouillet, Fabienne Giraud, Benjamin Guillet and Philippe Garrigue

US and EU radiopharmaceutical diagnostic and therapeutic nonclinical study requirements for clinical trials authorizations and marketing authorizations

New regulatory guidance documents from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recently been finalized or are in draft format outlining new pathways fo...

Authors: Sally W. Schwarz and Clemens Decristoforo

Comparison of desferrioxamine and NODAGA for the gallium-68 labeling of exendin-4

Radiolabeled exendin-4 (Ex4) derivatives are used to target the glucagon-like peptide-1 receptor (GLP-1R) for the clinical diagnosis of insulinomas, a rare type of neuroendocrine tumor. Gallium-68 is an ideal ...

Authors: Simon A. M. Kaeppeli, Roger Schibli, Thomas L. Mindt and Martin Behe

Endorsement of International Consensus Radiochemistry Nomenclature Guidelines

Authors: Philip Elsinga, Angelika Bischof Delaloye, Arturo Chiti, Stefaan Vandenberghe, Francesco Giammarile and Ignasi Carrio

Open letter to journal editors on: International Consensus Radiochemistry Nomenclature Guidelines

Authors: Heinz H. Coenen, Antony D. Gee, Michael Adam, Gunnar Antoni, Cathy S. Cutler, Yasuhisa Fujibayashi, Jae Min Jeong, Robert H. Mach, Thomas L. Mindt, Victor W. Pike and Albert D. Windhorst

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers

Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also gained attention in the...

Authors: Matteo Bauckneht, Selene Capitanio, Stefano Raffa, Luca Roccatagliata, Matteo Pardini, Caterina Lapucci, Cecilia Marini, Gianmario Sambuceti, Matilde Inglese, Paolo Gallo, Diego Cecchin, Flavio Nobili and Silvia Morbelli

Automated synthesis of [¹¹C]L-glutamine on Synthra HCN plus synthesis module

L-Glutamine (L-Gln) is the most abundant amino acid present in the human body and is involved in numerous metabolic pathways. Glutaminolysis is the metabolic process deployed by many aggressive cancers such as...

Authors: Prashanth K. Padakanti, Shihong Li, Alexander Schmitz, David Mankoff, Robert H. Mach and Hsiaoju S. Lee

Radiosynthesis and in vivo evaluation of ¹¹C-labeled BMS-193885 and its desmethyl analog as PET tracers for neuropeptide Y1 receptors

Neuropeptide Y (NPY) has been implicated in a wide variety of physiological processes, including feeding, learning, memory, emotion, cardiovascular homeostasis, hormone secretion, and circadian rhythms. NPY Yl...

Authors: Kazunori Kawamura, Wakana Mori, Masayuki Fujinaga, Tomoteru Yamasaki, Yiding Zhang, Hidekatsu Wakizaka, Akiko Hatori, Lin Xie, Katsushi Kumata, Takayuki Ohkubo, Yusuke Kurihara, Masanao Ogawa, Nobuki Nengaki and Ming-Rong Zhang

Radiochemical and analytical aspects of inter-institutional quality control measurements on radiopharmaceuticals

Clinically applied radiopharmaceuticals have to meet quality release criteria like a high radiochemical yield and radiochemical purity. Many radiopharmaceuticals do not have marketing authorization and have no...

Authors: Erik de Blois, Rory M. S. de Zanger, Ho Sze Chan, Mark Konijnenberg and Wouter A. P. Breeman

The new Regulation on clinical trials in relation to radiopharmaceuticals: when and how will it be implemented?

Authors: Iván Peñuelas, Daniëlle J. Vugts, Clemens Decristoforo and Philip H. Elsinga

Synthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression

The histological evaluation of estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer lesions from biopsy tissue can stratify patients to receive endocrine therapy. Furthermore, PR e...

Authors: Louis Allott, Cecilia Miranda, Angela Hayes, Florence Raynaud, Christopher Cawthorne and Graham Smith

An alternative methodology for the determination of the radiochemical purity of ¹¹C-methionine

[¹¹C]Methionine ([¹¹C]MET) acts as an oncological radiopharmaceutical for measuring increased protein synthesis in brain tumours while having low uptake in normal brain an. In several Latin American countries, th...

Authors: Javier Giglio, Gabriela Rosas, Martín Basso, Andrea Boné, Eduardo Savio and Henry Engler

A high molar activity ¹⁸F-labeled TAK-875 derivative for PET imaging of pancreatic β-cells

The free-fatty acid receptor-1 (FFA-1) is expressed by β-cells and is a promising target for molecular imaging of functional β-cell mass. Recently, the ((3-[¹⁸F]fluoropropyl)sulfonyl)propoxy-derivative of the hig...

Authors: Mark H. Dornan, Daniil Petrenyov, José-Mathieu Simard, Antonio Aliaga, Guoming Xiong, Julien Ghislain, Barry Bedell, Vincent Poitout and Jean N. DaSilva