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Synthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET EJNMMI Radiopharm. Chem. Pub Date : 2024-03-06 Eva Schlein, Johanna Rokka, Luke R. Odell, Sara Lopes van den Broek, Matthias M. Herth, Umberto M. Battisti, Stina Syvänen, Dag Sehlin, Jonas Eriksson
The brain is a challenging target for antibody-based positron emission tomography (immunoPET) imaging due to the restricted access of antibody-based ligands through the blood–brain barrier (BBB). To overcome this physiological obstacle, we have previously developed bispecific antibody ligands that pass through the BBB via receptor-mediated transcytosis. While these radiolabelled ligands have high affinity
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Preclinical characterisation of gallium-68 labeled ferrichrome siderophore stereoisomers for PET imaging applications EJNMMI Radiopharm. Chem. Pub Date : 2024-03-04 Kristyna Krasulova, Barbora Neuzilova, Katerina Dvorakova Bendova, Zbynek Novy, Miroslav Popper, Marian Hajduch, Milos Petrik
Siderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target the pathophysiological mechanisms of pathogens. Gallium-68 can replace the iron in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific
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A novel PET probe to selectively image heat shock protein 90α/β isoforms in the brain EJNMMI Radiopharm. Chem. Pub Date : 2024-03-04 Takayuki Sakai, Aya Ogata, Hiroshi Ikenuma, Takashi Yamada, Saori Hattori, Junichiro Abe, Shinichi Imamura, Masanori Ichise, Mari Tada, Akiyoshi Kakita, Hiroko Koyama, Masaaki Suzuki, Takashi Kato, Kengo Ito, Yasuyuki Kimura
Heat shock proteins (HSPs) are present throughout the brain. They function as molecular chaperones, meaning they help with the folding and unfolding of large protein complexes. These chaperones are vital in the development of neuropathological conditions such as Alzheimer’s disease and Lewy body disease, with HSP90, a specific subtype of HSP, playing a key role. Many studies have shown that drugs that
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Preclinical comparison of [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2 for endoradiotherapy of prostate cancer: biodistribution and dosimetry studies EJNMMI Radiopharm. Chem. Pub Date : 2024-02-26 Alexander Wurzer, Francesco De Rose, Sebastian Fischer, Markus Schwaiger, Wolfgang Weber, Stephan Nekolla, Hans-Jürgen Wester, Matthias Eiber, Calogero D’Alessandria
Radiohybrid PSMA-targeted ligands (rhPSMA) have been introduced as a novel platform for theranostic applications. Among a variety of rhPSMA-ligands developed for radioligand therapy, two stereoisomers [177Lu]Lu-rhPSMA-10.1 and -10.2 have been synthesized and initially characterized in preclinical experiments with the aim to provide an optimized binding profile to human serum albumin, a reduction of
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Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics EJNMMI Radiopharm. Chem. Pub Date : 2024-02-26 Yuta Kaizuka, Hiroyuki Suzuki, Tadashi Watabe, Kazuhiro Ooe, Atsushi Toyoshima, Kazuhiro Takahashi, Koichi Sawada, Takashi Iimori, Yoshitada Masuda, Takashi Uno, Kento Kannaka, Tomoya Uehara
L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, 211At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211At for radiotherapy. In this study, radiohalogen-labeled amino
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Radiosynthesis, structural identification and in vitro tissue binding study of [18F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3 EJNMMI Radiopharm. Chem. Pub Date : 2024-02-23 Pyry Dillemuth, Tuomas Karskela, Abiodun Ayo, Jesse Ponkamo, Jonne Kunnas, Johan Rajander, Olli Tynninen, Anne Roivainen, Pirjo Laakkonen, Anu J. Airaksinen, Xiang-Guo Li
Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate
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Optimization and scale up of production of the PSMA imaging agent [18F]AlF-P16-093 on a custom automated radiosynthesis platform EJNMMI Radiopharm. Chem. Pub Date : 2024-02-23 David Alexoff, Seok Rye Choi, Karl Ploessl, Dohyun Kim, Ruiyue Zhao, Lin Zhu, Hank Kung
Recent advancements in positron emission tomograph (PET) using prostate specific membrane antigen (PSMA)-targeted radiopharmaceuticals have changed the standard of care for prostate cancer patients by providing more accurate information during staging of primary and recurrent disease. [68Ga]Ga-P16-093 is a new PSMA-PET radiopharmaceutical that demonstrated superior imaging performance in recent head-to-head
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Chelator impact: investigating the pharmacokinetic behavior of copper-64 labeled PD-L1 radioligands EJNMMI Radiopharm. Chem. Pub Date : 2024-02-19 Fabian Krutzek, Cornelius K. Donat, Sven Stadlbauer
Programmed cell death ligand 1 (PD-L1) plays a critical role in the tumor microenvironment and overexpression in several solid cancers has been reported. This was associated with a downregulation of the local immune response, specifically of T-cells. Immune checkpoint inhibitors showed a potential to break this localized immune paralysis, but only 30% of patients are considered responders. New diagnostic
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Preclinical evaluation of new GRPR-antagonists with improved metabolic stability for radiotheranostic use in oncology EJNMMI Radiopharm. Chem. Pub Date : 2024-02-16 Panagiotis Kanellopoulos, Adam Mattsson, Ayman Abouzayed, Karim Obeid, Berthold A. Nock, Vladimir Tolmachev, Theodosia Maina, Anna Orlova
The gastrin-releasing peptide receptor (GRPR) has been extensively studied as a biomolecular target for peptide-based radiotheranostics. However, the lack of metabolic stability and the rapid clearance of peptide radioligands, including radiolabeled GRPR-antagonists, often impede clinical application. Aiming at circumventing these drawbacks, we have designed three new GRPR-antagonist radioligands using
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Intranasal administration enhances size-dependent pulmonary phagocytic uptake of poly(lactic-co-glycolic acid) nanoparticles EJNMMI Radiopharm. Chem. Pub Date : 2024-02-15 Seung Ho Baek, Eun-Ha Hwang, Gyeung Haeng Hur, Green Kim, You Jung An, Jae-Hak Park, Jung Joo Hong
Nanoparticles exhibit distinct behaviours within the body, depending on their physicochemical properties and administration routes. However, in vivo behaviour of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, especially when administered nasally, remains unexplored; furthermore, there is a lack of comparative analysis of uptake efficiency among different administration routes. Therefore, here
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Validation of an automated dispensing system for subsequent dose dispensing of different radionuclides EJNMMI Radiopharm. Chem. Pub Date : 2024-02-12 T. T. Cao, E. A. Aalbersberg, M. M. Geluk-Jonker, J. J. M. A. Hendrikx
Automated dispensing systems (ADSs) for radiopharmaceuticals have been developed to reduce the radiation exposure of personnel, to improve the accuracy of the dispensed dose and to limit the microbiological contamination. However, before implementing such systems, validation according to various applicable guidelines is necessary to ensure safety and quality. Here we present the selection, validation
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Improved synthesis of 6-bromo-7-[11C]methylpurine for clinical use EJNMMI Radiopharm. Chem. Pub Date : 2024-02-09 Toshimitsu Okamura, Tatsuya Kikuchi, Masanao Ogawa, Ming-Rong Zhang
Multidrug resistance-associated protein 1 (MRP1), an energy-dependent efflux pump, is expressed widely in various tissues and contributes to many physiological and pathophysiological processes. 6-Bromo-7-[11C]methylpurine ([11C]7m6BP) is expected to be useful for the assessment of MRP1 activity in the human brain and lungs. However, the radiochemical yield (RCY) in the synthesis of [11C]7m6BP was low
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Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives EJNMMI Radiopharm. Chem. Pub Date : 2024-02-06 Eline L. Hooijman, Valery Radchenko, Sui Wai Ling, Mark Konijnenberg, Tessa Brabander, Stijn L. W. Koolen, Erik de Blois
In the past years, there has been a notable increase in interest regarding targeted alpha therapy using Ac-225, driven by the observed promising clinical anti-tumor effects. As the production and technology has advanced, the availability of Ac-225 is expected to increase in the near future, making the treatment available to patients worldwide. Ac-225 can be labelled to different biological vectors
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Unnatural amino acid substitutions to improve in vivo stability and tumor uptake of 68Ga-labeled GRPR-targeted TacBOMB2 derivatives for cancer imaging with positron emission tomography EJNMMI Radiopharm. Chem. Pub Date : 2024-02-02 Lei Wang, Hsiou-Ting Kuo, Zhengxing Zhang, Chengcheng Zhang, Chao-Cheng Chen, Devon Chapple, Ryan Wilson, Nadine Colpo, François Bénard, Kuo-Shyan Lin
Overexpressed in various solid tumors, gastrin-releasing peptide receptor (GRPR) is a promising cancer imaging marker and therapeutic target. Although antagonists are preferable for the development of GRPR-targeted radiopharmaceuticals due to potentially fewer side effects, internalization of agonists may lead to longer tumor retention and better treatment efficacy. In this study, we systematically
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A novel PSMA-targeting tracer with highly negatively charged linker demonstrates decreased salivary gland uptake in mice compared to [68Ga]Ga-PSMA-11 EJNMMI Radiopharm. Chem. Pub Date : 2024-01-30 Steve S. Huang, Frank P. DiFilippo, Daniel J. Lindner, Warren D. Heston
The current generation of radiolabeled PSMA-targeting therapeutic agents is limited by prominent salivary gland binding, which results in dose-limiting xerostomia from radiation exposure. JB-1498 is a urea-based small molecule with a highly negatively charged linker targeting prostate specific membrane antigen (PSMA). Prior work on a similar tracer with the same negatively charged linker demonstrated
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Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding EJNMMI Radiopharm. Chem. Pub Date : 2024-01-22 Ali Fele-Paranj, Babak Saboury, Carlos Uribe, Arman Rahmim
We aimed to develop a publicly shared computational physiologically based pharmacokinetic (PBPK) model to reliably simulate and analyze radiopharmaceutical therapies (RPTs), including probing of hot-cold ligand competitions as well as alternative injection scenarios and drug designs, towards optimal therapies. To handle the complexity of PBPK models (over 150 differential equations), a scalable modeling
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Preclinical evaluation of the theranostic potential of 89Zr/177Lu-labeled anti-TROP-2 antibody in triple-negative breast cancer model EJNMMI Radiopharm. Chem. Pub Date : 2024-01-09 Yitian Wu, Tuo li, Xianzhong Zhang, Hongli Jing, Fang Li, Li Huo
Triple-negative breast cancer (TNBC) is one of the most lethal malignant tumors among women, characterized by high invasiveness, high heterogeneity, and lack of specific therapeutic targets such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Trophoblast cell-surface antigen-2 (TROP-2) is a transmembrane glycoprotein over-expressed in 80% of TNBC patients
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Cu(II)-Mediated direct 18F-dehydrofluorination of phosphine oxides in high molar activity EJNMMI Radiopharm. Chem. Pub Date : 2024-01-06 Xiaoqun Tang, Shengji Lv, Zhaobiao Mou, Xia Liu, Zijing Li
The 18F/19F-isotope exchange method employing P(V)-centered prosthetic groups demonstrates advantages in addressing mild one-step aqueous 18F-labeling of peptides and proteins. However, the molar activity (Am) achieved through isotope exchange remains relatively low, unless employing a high initial activity of [18F]F−. To overcome this drawback, our work introduces a novel approach through a Cu-mediated
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Production of the PET radionuclide 61Cu via the 62Ni(p,2n)61Cu nuclear reaction EJNMMI Radiopharm. Chem. Pub Date : 2024-01-05 Santiago Andrés Brühlmann, Martin Walther, Klaus Kopka, Martin Kreller
There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio 61Cu, 64Cu and 67Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide
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Position paper to facilitate patient access to radiopharmaceuticals: considerations for a suitable pharmaceutical regulatory framework EJNMMI Radiopharm. Chem. Pub Date : 2024-01-02 Aruna Korde, Marianne Patt, Svetlana V. Selivanova, Andrew M. Scott, Rolf Hesselmann, Oliver Kiss, Natesan Ramamoorthy, Sergio Todde, Sietske M. Rubow, Luther Gwaza, Serge Lyashchenko, Jan Andersson, Brian Hockley, Ravindra Kaslival, Clemens Decristoforo
Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals. This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These
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Preclinical evaluation of an 18F-labeled Nε-acryloyllysine piperazide for covalent targeting of transglutaminase 2 EJNMMI Radiopharm. Chem. Pub Date : 2024-01-02 Robert Wodtke, Markus Laube, Sandra Hauser, Sebastian Meister, Friedrich-Alexander Ludwig, Steffen Fischer, Klaus Kopka, Jens Pietzsch, Reik Löser
Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associated TGase 2, and targeted covalent inhibitors appear to be particularly
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Chromatographic separation of silver-111 from neutron-irradiated palladium target: toward direct labeling of radiotracers EJNMMI Radiopharm. Chem. Pub Date : 2023-12-20 Marianna Tosato, Andrea Gandini, Steffen Happel, Marine Bas, Antonietta Donzella, Aldo Zenoni, Andrea Salvini, Alberto Andrighetto, Valerio Di Marco, Mattia Asti
Silver-111 is a promising β−-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the
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Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer EJNMMI Radiopharm. Chem. Pub Date : 2023-12-13 Hemantha Mallapura, Olga Ovdiichuk, Emma Jussing, Tran A. Thuy, Camille Piatkowski, Laurent Tanguy, Charlotte Collet-Defossez, Bengt Långström, Christer Halldin, Sangram Nag
The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged
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Optimized, automated and cGMP-compliant synthesis of the HER2 targeting [68Ga]Ga-ABY-025 tracer EJNMMI Radiopharm. Chem. Pub Date : 2023-11-22 Emma Jussing, Mélodie Ferrat, Mohammad M. Moein, Henrik Alfredéen, Tetyana Tegnebratt, Klas Bratteby, Erik Samén, Joachim Feldwisch, Renske Altena, Rimma Axelsson, Thuy A. Tran
The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (111In) or gallium-68 (68Ga). Using the latter, 68Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to 111In. For an ongoing phase II study
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Metallacages with 2,6-dipicolinoylbis(N,N-dialkylthioureas) as novel platforms in nuclear medicine for 68Ga, 177Lu and 198Au EJNMMI Radiopharm. Chem. Pub Date : 2023-11-20 Anna Baitullina, Guilhem Claude, Suelen F. Sucena, Eda Nisli, Cedric Scholz, Punita Bhardwaj, Holger Amthauer, Winfried Brenner, Christopher Geppert, Christian Gorges, Ulrich Abram, Pedro Ivo da Silva Maia, Sarah Spreckelmeyer
Heterometallic gold metallacages are of great interest for the incorporation of several cations. Especially in nuclear medicine, those metallacages can serve as a platform for radionuclides relevant for imaging or therapy (e.g. 68Ga or 177Lu). Moreover, the radionuclide 198Au is an attractive beta emitter, for potential application in nuclear medicine. Here, we aim to synthesize a new set of gold metallacages
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Proceedings of international symposium of trends in radiopharmaceuticals 2023 (ISTR-2023) EJNMMI Radiopharm. Chem. Pub Date : 2023-11-10 Amirreza Jalilian, Clemens Decristoforo, Melissa Denecke, Philip H. Elsinga, Cornelia Hoehr, Aruna Korde, Suzanne E. Lapi, Peter J. H. Scott
The International Atomic Energy Agency (IAEA) held the 3rd International Symposium on Trends in Radiopharmaceuticals, (ISTR-2023) at IAEA Headquarters in Vienna, Austria, during the week of 16–21 April 2023. This procedural paper summarizes highlights from symposium presentations, posters, panel discussions and satellite meetings, and provides additional resources that may be useful to researchers
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The Curies’ element: state of the art and perspectives on the use of radium in nuclear medicine EJNMMI Radiopharm. Chem. Pub Date : 2023-11-10 Sara Franchi, Mattia Asti, Valerio Di Marco, Marianna Tosato
The alpha-emitter radium-223 (223Ra) is presently used in nuclear medicine for the palliative treatment of bone metastases from castration-resistant prostate cancer. This application arises from its advantageous decay properties and its intrinsic ability to accumulate in regions of high bone turnover when injected as a simple chloride salt. The commercial availability of [223Ra]RaCl2 as a registered
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Evaluation of the 177mLu-concentration in in-house produced 177Lu-radiopharmaceuticals and commercially available Lutathera® EJNMMI Radiopharm. Chem. Pub Date : 2023-11-06 Matthias Balzer, Fleur Spiecker, Stephanie Bluemel, Holger Amthauer, Winfried Brenner, Sarah Spreckelmeyer
177Lu-radiopharmaceuticals can contain the metastable impurity [177mLu]lutetium with a physical half-life of 160.4 days, in varying concentrations depending on the route of production of the radionuclidic precursor [177Lu]lutetium. Due to the long half-life of [177mLu]lutetium, difficulties with waste disposal or sterility testing could arise. Here, we analyzed several 177Lu-samples of different origins
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89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations EJNMMI Radiopharm. Chem. Pub Date : 2023-11-06 Maryke Kahts, Hua Guo, Harikrishna Kommidi, Yanping Yang, Haluk Burcak Sayman, Beverley Summers, Richard Ting, Jan Rijn Zeevaart, Mike Sathekge, Omer Aras
The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here
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Highlight selection of radiochemistry and radiopharmacy developments by editorial board EJNMMI Radiopharm. Chem. Pub Date : 2023-10-27 Jean DaSilva, Clemens Decristoforo, Robert H. Mach, Guy Bormans, Giuseppe Carlucci, Mohammed Al-Qahtani, Adriano Duatti, Antony D. Gee, Wiktor Szymanski, Sietske Rubow, Jeroen Hendrikx, Xing Yang, Hongmei Jia, Junbo Zhang, Peter Caravan, Hua Yang, Jan Rijn Zeevaart, Miguel Avila Rodriquez, Ralph Santos Oliveira, Marcela Zubillaga, Tamer Sakr, Sarah Spreckelmeyer
The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application
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Bacterial survival in radiopharmaceutical solutions: a critical impact on current practices EJNMMI Radiopharm. Chem. Pub Date : 2023-10-26 Julien Leenhardt, Luc Choisnard, Maelle Plasse, Valérie Ardisson, Nicolas de Leiris, Loic Djaileb, Pierrick Bedouch, Marie-Dominique Brunet
The aim of this brief communication is to highlight the potential bacteriological risk linked to the processes control of radiopharmaceutical preparations made in a radiopharmacy laboratory. Survival rate of Pseudomonas aeruginosa (ATCC: 27853) or Staphylococcus aureus (ATCC: 25923) or Staphylococcus epidermidis (ATCC: 1228) in multidose technetium-99 m solution was studied. Depending on the nature
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Dosimetry of [18F]TRACK, the first PET tracer for imaging of TrkB/C receptors in humans EJNMMI Radiopharm. Chem. Pub Date : 2023-10-23 Alexander Thiel, Alexey Kostikov, Hailey Ahn, Youstina Daoud, Jean-Paul Soucy, Stephan Blinder, Carolin Jaworski, Carmen Wängler, Björn Wängler, Freimut Juengling, Shirin A. Enger, Ralf Schirrmacher
Reduced expression or impaired signalling of tropomyosin receptor kinases (Trk receptors) are found in a vast spectrum of CNS disorders. [18F]TRACK is the first PET radioligand for TrkB/C with proven in vivo brain penetration and on-target specific signal. Here we report dosimetry data for [18F]TRACK in healthy humans. 6 healthy participants (age 22–61 y, 3 female) were scanned on a General Electric
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TrisOxine abiotic siderophores for technetium complexation: radiolabeling and biodistribution studies EJNMMI Radiopharm. Chem. Pub Date : 2023-10-19 Julien Leenhardt, Alexandre Biguet Petit Jean, Florian Raes, Emilien N’Guessan, Marlène Debiossat, Clémence André, Sandrine Bacot, Mitra Ahmadi, Nicolas de Leiris, Loïc Djaileb, Catherine Ghezzi, Marie-Dominique Brunet, Alexis Broisat, Pascale Perret, Amaury du Moulinet d’Hardemare
Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as
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Synthesis and evaluation of a novel PET ligand, a GSK’963 analog, aiming at autoradiography and imaging of the receptor interacting protein kinase 1 in the brain EJNMMI Radiopharm. Chem. Pub Date : 2023-10-18 Hiroshi Ikenuma, Aya Ogata, Hiroko Koyama, Bin Ji, Hideki Ishii, Takashi Yamada, Junichiro Abe, Chie Seki, Yuji Nagai, Masanori Ichise, Takafumi Minamimoto, Makoto Higuchi, Ming-Rong Zhang, Takashi Kato, Kengo Ito, Masaaki Suzuki, Yasuyuki Kimura
Receptor interacting protein kinase 1 (RIPK1) is a serine/threonine kinase, which regulates programmed cell death and inflammation. Recently, the involvement of RIPK1 in the pathophysiology of Alzheimer’s disease (AD) has been reported; RIPK1 is involved in microglia’s phenotypic transition to their dysfunctional states, and it is highly expressed in the neurons and microglia in the postmortem brains
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Fully automated radiolabeling of [68Ga]Ga-EMP100 targeting c-MET for PET-CT clinical imaging EJNMMI Radiopharm. Chem. Pub Date : 2023-10-16 Timofei Rusu, Matthieu Delion, Charlotte Pirot, Amaury Blin, Anita Rodenas, Jean-Noël Talbot, Nicolas Veran, Christophe Portal, Françoise Montravers, Jacques Cadranel, Aurélie Prignon
c-MET is a transmembrane receptor involved in many biological processes and contributes to cell proliferation and migration during cancer invasion process. Its expression is measured by immunehistochemistry on tissue biopsy in clinic, although this technique has its limitations. PET-CT could allow in vivo mapping of lesions expressing c-MET, providing whole-body detection. A number of radiopharmaceuticals
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Fully automated radiosynthesis of [68Ga]Ga-FAPI-46 with cyclotron produced gallium EJNMMI Radiopharm. Chem. Pub Date : 2023-10-16 Adam J. Rosenberg, Yiu-Yin Cheung, Fei Liu, Carina Sollert, Todd E. Peterson, Jonathan A. Kropski
Radiopharmaceuticals capable of targeting the fibroblast activation protein have become widely utilized in the research realm as well as show great promise to be commercialized; with [68Ga]Ga-FAPI-46 being one of the most widely utilized. Until now the synthesis has relied on generator-produced gallium-68. Here we present a developed method to utilize liquid-target cyclotron-produced gallium-68 to
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State of the art procedures towards reactive [18F]fluoride in PET tracer synthesis EJNMMI Radiopharm. Chem. Pub Date : 2023-10-12 Lizeth Y. F. Haveman, Danielle J. Vugts, Albert D. Windhorst
Positron emission tomography (PET) is a powerful, non-invasive preclinical and clinical nuclear imaging technique used in disease diagnosis and therapy assessment. Fluorine-18 is the predominant radionuclide used for PET tracer synthesis. An impressive variety of new ‘late-stage’ radiolabeling methodologies for the preparation of 18F-labeled tracers has appeared in order to improve the efficiency of
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Novel radionuclides for use in Nuclear Medicine in Europe: where do we stand and where do we go? EJNMMI Radiopharm. Chem. Pub Date : 2023-10-12 Maija Radzina, Laura Saule, Edgars Mamis, Ulli Koester, Thomas Elias Cocolios, Elina Pajuste, Marika Kalnina, Kristaps Palskis, Zoe Sawitzki, Zeynep Talip, Mikael Jensen, Charlotte Duchemin, Kirsten Leufgen, Thierry Stora
In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe. A consortium
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Au@109Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers: studies on the applicability of 109Pd/109mAg in vivo generator in combined β− auger electron therapy EJNMMI Radiopharm. Chem. Pub Date : 2023-10-11 Nasrin Abbasi Gharibkandi, Kamil Wawrowicz, Agnieszka Majkowska-Pilip, Kinga Żelechowska-Matysiak, Mateusz Wierzbicki, Aleksander Bilewicz
In radionuclide therapy, to enhance therapeutic efficacy, an intriguing alternative is to ensure the simultaneous implementation of low- and high-LET radiation emitted from a one radionuclide. In the present study, we introduce the concept of utilizing 109Pd (T1/2 = 13.7 h) in the form of a 109Pd/109mAg in vivo generator. In this system, 109Pd emits beta particles of medium energy, while 109mAg releases
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Good practices for the automated production of 18F-SiFA radiopharmaceuticals EJNMMI Radiopharm. Chem. Pub Date : 2023-10-11 Simon Blok, Carmen Wängler, Peter Bartenstein, Klaus Jurkschat, Ralf Schirrmacher, Simon Lindner
The positron emitting isotope fluorine-18 (18F) possesses almost ideal physicochemical properties for the development of radiotracers for diagnostic molecular imaging employing positron emission tomography (PET). 18F in its nucleophilic anionic 18F− form is usually prepared by bombarding an enriched 18O water target with protons of various energies between 5 and 20 MeV depending on the technical specifications
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[225Ac]Ac- and [111In]In-DOTA-trastuzumab theranostic pair: cellular dosimetry and cytotoxicity in vitro and tumour and normal tissue uptake in vivo in NRG mice with HER2-positive human breast cancer xenografts EJNMMI Radiopharm. Chem. Pub Date : 2023-09-26 Misaki Kondo, Zhongli Cai, Conrad Chan, Nubaira Forkan, Raymond M. Reilly
Trastuzumab (Herceptin) has improved the outcome for patients with HER2-positive breast cancer (BC) but brain metastases (BM) remain a challenge due to poor uptake of trastuzumab into the brain. Radioimmunotherapy (RIT) with trastuzumab labeled with α-particle emitting, 225Ac may overcome this challenge by increasing the cytotoxic potency on HER2-positive BC cells. Our first aim was to synthesize and
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Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β EJNMMI Radiopharm. Chem. Pub Date : 2023-09-21 Olivia Wegrzyniak, Bo Zhang, Johanna Rokka, Maria Rosestedt, Bogdan Mitran, Pierre Cheung, Emmi Puuvuori, Sofie Ingvast, Jonas Persson, Helena Nordström, John Löfblom, Fredrik Pontén, Fredrik Y. Frejd, Olle Korsgren, Jonas Eriksson, Olof Eriksson
Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([18F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis. In vitro
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Development of [225Ac]Ac-DOTA-C595 as radioimmunotherapy of pancreatic cancer: in vitro evaluation, dosimetric assessment and detector calibration EJNMMI Radiopharm. Chem. Pub Date : 2023-09-07 Ashleigh Hull, William Hsieh, Artem Borysenko, William Tieu, Dylan Bartholomeusz, Eva Bezak
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy which may benefit from radioimmunotherapy. Previously, [177Lu]Lu-DOTA-C595 has been developed as a beta-emitting radioimmunoconjugate to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on PDAC. However, the therapeutic effect may be enhanced by using an alpha-emitting radionuclide such as Actinium-225 (Ac-225). The
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Reducing kidney uptake of radiolabelled exendin-4 using variants of the renally cleavable linker MVK EJNMMI Radiopharm. Chem. Pub Date : 2023-09-04 Belinda Trachsel, Giulia Valpreda, Alexandra Lutz, Roger Schibli, Linjing Mu, Martin Béhé
Peptidic radiotracers are preferentially excreted through the kidneys, which often results in high persistent renal retention of radioactivity, limiting or even preventing therapeutic clinical translation of these radiotracers. Exendin-4, which targets the glucagon-like-peptide 1 receptor (GLP-1R) overexpressed in insulinomas and in congenital hyperinsulinism, is an example thereof. The use of the
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First-in-human study of a novel cell death tracer [99mTc]Tc-Duramycin: safety, biodistribution and radiation dosimetry in healthy volunteers EJNMMI Radiopharm. Chem. Pub Date : 2023-08-30 Taco Metelerkamp Cappenberg, Stijn De Schepper, Christel Vangestel, Stef De Lombaerde, Leonie wyffels, Tim Van den Wyngaert, Jeffrey Mattis, Brian Gray, Koon Pak, Sigrid Stroobants, Filipe Elvas
Imaging of cell death can provide an early indication of treatment response in cancer. [99mTc]Tc-Duramycin is a small-peptide SPECT tracer that recognizes both apoptotic and necrotic cells by binding to phosphatidylethanolamine present in the cell membrane. Preclinically, this tracer has shown to have favorable pharmacokinetics and selective tumor accumulation early after the onset of anticancer therapy
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Evaluation of the pharmacokinetics, dosimetry, and therapeutic efficacy for the α-particle-emitting transarterial radioembolization (αTARE) agent [225Ac]Ac-DOTA-TDA-Lipiodol® against hepatic tumors EJNMMI Radiopharm. Chem. Pub Date : 2023-08-14 Anders Josefsson, Angel G. Cortez, Harikrishnan Rajkumar, Joseph D. Latoche, Ambika P. Jaswal, Kathryn E. Day, Mohammadreza Zarisfi, Lora H. Rigatti, Ziyu Huang, Jessie R. Nedrow
The liver is a common site for metastatic disease for a variety of cancers, including colorectal cancer. Both primary and secondary liver tumors are supplied through the hepatic artery while the healthy liver is supplied by the portal vein. Transarterial radioembolization (TARE) using yttrium-90 glass or resin microspheres have shown promising results with reduced side-effects but have similar survival
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In vitro characterisation of [177Lu]Lu-DOTA-C595 as a novel radioimmunotherapy for MUC1-CE positive pancreatic cancer EJNMMI Radiopharm. Chem. Pub Date : 2023-08-14 Ashleigh Hull, William Hsieh, William Tieu, Dylan Bartholomeusz, Yanrui Li, Eva Bezak
Pancreatic ductal adenocarcinoma (PDAC) continues to be a malignancy with an unmet clinical demand. Development of radioimmunoconjugates which target cancer-specific receptors provides an opportunity for radioimmunotherapy of both metastatic and primary PDAC. In this study, we characterised the in vitro behaviour of a novel beta-emitting radioimmunoconjugate [177Lu]Lu-DOTA-C595 as a therapeutic agent
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The DOTA macrocyclic cavity in metallic radiopharmaceuticals: Mythology or reality? EJNMMI Radiopharm. Chem. Pub Date : 2023-08-03 Adriano Duatti
The hypothetical concept of ‘macrocyclic cavity’ is largely employed as useful model to interpret the affinity of metal ions for the macrocyclic chelating ligand 2,2′,2′′,2′′′-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (H4DOTA). It Is hypothesized that a close matching between the size of the macrocyclic cavity and that of the metallic ion is a key parameter to ensure the high-yield
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EJNMMI Radiopharmacy and Chemistry obtains its first impact factor!! EJNMMI Radiopharm. Chem. Pub Date : 2023-07-25 Philip H. Elsinga
EJNMMI Radiopharmacy and Chemistry has obtained its first Impact factor by Clarivate. The journal is now fully indexed and listed in all relevant databases, a list of the indexing services where the journal is included is available at https://ejnmmipharmchem.springeropen.com/about. The Impact Factor 2022 of EJNMMI Radiopharmacy and Chemistry is 4.6. The journal is included in the following JCR categories:
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Simplified and highly-reliable automated production of [18F]FSPG for clinical studies EJNMMI Radiopharm. Chem. Pub Date : 2023-07-24 Mai Lin, Robert T. Ta, H. Charles Manning
(S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc−), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer
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Automated radiosynthesis and in vivo evaluation of 18F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy EJNMMI Radiopharm. Chem. Pub Date : 2023-07-17 Kazunori Kawamura, Tomoteru Yamasaki, Masayuki Fujinaga, Tomomi Kokufuta, Yiding Zhang, Wakana Mori, Yusuke Kurihara, Masanao Ogawa, Kaito Tsukagoe, Nobuki Nengaki, Ming-Rong Zhang
A family of BF2-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring. Radiolabeled photosensitizers can efficiently address photosensitizer biodistribution
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First preclinical evaluation of [225Ac]Ac-DOTA-JR11 and comparison with [177Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs EJNMMI Radiopharm. Chem. Pub Date : 2023-06-30 Maryana Handula, Savanne Beekman, Mark Konijnenberg, Debra Stuurman, Corrina de Ridder, Frank Bruchertseifer, Alfred Morgenstern, Antonia Denkova, Erik de Blois, Yann Seimbille
The [177Lu]Lu-DOTA-TATE mediated peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) is sometimes leading to treatment resistance and disease recurrence. An interesting alternative could be the somatostatin antagonist, [177Lu]Lu-DOTA-JR11, that demonstrated better biodistribution profile and higher tumor uptake than [177Lu]Lu-DOTA-TATE. Furthermore, treatment with alpha emitters
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Abstracts from the 20th European symposium on radiopharmacy and radiopharmaceuticals EJNMMI Radiopharm. Chem. Pub Date : 2023-06-15
Combined radionuclide and hyperthermia cancer therapy with superparamagnetic iron oxide nanoparticles coupled to 131I-labeled antibodies Aljoša Stanković1, Marija Mirković2, Magdalena Radović2, Zorana Milanović2, Aleksandar Vukadinović2, Drina Janković2, Sanja Vranješ-Đurić2 1University Clinical Centre of the Republic of Srpska, Clinical Department for Nuclear Medicine and Thyroid Gland Disease, Bosnia
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Intravenous and oral whole body ketone dosimetry, biodistribution, metabolite correction and kinetics studied by (R)-[1-11C]β-hydroxybutyrate ([11C]OHB) PET in healthy humans EJNMMI Radiopharm. Chem. Pub Date : 2023-06-14 Thien Vinh Luong, Erik Nguyen Nielsen, Lise Falborg, Mette Louise Gram Kjærulff, Lars Poulsen Tolbod, Esben Søndergaard, Niels Møller, Ole Lajord Munk, Lars Christian Gormsen
Ketones are increasingly recognized as an important and possibly oxygen sparing source of energy in vital organs such as the heart, the brain and the kidneys. Drug treatments, dietary regimens and oral ketone drinks designed to deliver ketones for organ and tissue energy production have therefore gained popularity. However, whether ingested ketones are taken up by various extra-cerebral tissues and
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Optimization of 177Lu-labelling of DOTA-TOC, PSMA-I&T and FAPI-46 for clinical application EJNMMI Radiopharm. Chem. Pub Date : 2023-05-26 Aylin Cankaya, Matthias Balzer, Holger Amthauer, Winfried Brenner, Sarah Spreckelmeyer
177Lu-radiopharmaceuticals are routinely used for the treatment of various tumor entities. The productions of radiopharmaceuticals follow strict good-manufacturing practice guidelines and synthesis optimizations thereof have a strong impact on e.g. the quality of the product, radiation safety and costs. The purpose of this study is to optimize the precursor load of three radiopharmaceuticals. For that
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Membrane-based microfluidic solvent extraction of Ga-68 from aqueous Zn solutions: towards an automated cyclotron production loop EJNMMI Radiopharm. Chem. Pub Date : 2023-05-05 Svenja Trapp, Tom Lammers, Gokce Engudar, Cornelia Hoehr, Antonia G. Denkova, Elisabeth Paulssen, Robin M. de Kruijff
The radionuclide Ga-68 is commonly used in nuclear medicine, specifically in positron emission tomography (PET). Recently, the interest in producing Ga-68 by cyclotron irradiation of [68Zn]Zn nitrate liquid targets is increasing. However, current purification methods of Ga-68 from the target solution consist of multi-step procedures, thus, leading to a significant loss of activity through natural decay
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Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models EJNMMI Radiopharm. Chem. Pub Date : 2023-04-24 Jonatan Dewulf, Tal Flieswasser, Tim Delahaye, Christel Vangestel, Alan Miranda, Hans de Haard, Julie Jacobs, Evelien Smits, Tim Van den Wyngaert, Filipe Elvas
CD70-CD27 is a costimulatory ligand-receptor pair in the tumor necrosis factor receptor family. With only limited expression in normal tissues, CD70 is constitutively expressed in a variety of solid tumors and hematologic malignancies, facilitating immunosuppression through CD27 signaling in the tumor microenvironment by enhanced survival of regulatory T cells, induction of T cell apoptosis, and T
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Improved quality control of [177Lu]Lu-PSMA I&T EJNMMI Radiopharm. Chem. Pub Date : 2023-03-27 Martin Kraihammer, Piotr Garnuszek, Andreas Bauman, Michael Maurin, Manuel Alejandre Lafont, Roland Haubner, Elisabeth von Guggenberg, Michael Gabriel, Clemens Decristoforo
Targeted radionuclide therapy with [177Lu]Lu-PSMA I&T (zadavotide guraxetan) has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide. Several methods to determine the radiochemical purity have been reported but also limitations in the HPLC analysis due to retention of the sample and tailing effects when using standard gradients containing trifluoroacetic acid
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Highlight selection of radiochemistry and radiopharmacy developments by editorial board EJNMMI Radiopharm. Chem. Pub Date : 2023-03-23 Oliver C. Kiss, Peter J. H. Scott, Martin Behe, Ivan Penuelas, Jan Passchier, Ana Rey, Marianne Patt, Silvio Aime, Amir Jalilian, Peter Laverman, Zhen Cheng, Alain Faivre Chauvet, Jonathan Engle, Frederik Cleeren, Hua Zhu, Johnny Vercouillie, Michael van Dam, Ming Rong Zhang, Lars Perk, Benjamin Guillet, Francisco Alves
The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application
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Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist’s perspective EJNMMI Radiopharm. Chem. Pub Date : 2023-03-10 Torsten Kniess, Jörg Zessin, Peter Mäding, Manuela Kuchar, Oliver Kiss, Klaus Kopka
[18F]fluoromisonidazole ([18F]FMISO, 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [18F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy. Since the introduction of [18F]FMISO as positron