-
Good practices for 89Zr radiopharmaceutical production and quality control EJNMMI Radiopharm. Chem. Pub Date : 2024-05-11 Thomas Erik Wuensche, Serge Lyashchenko, Guus A. M. S. van Dongen, Danielle Vugts
During the previous two decades, PET imaging of biopharmaceuticals radiolabeled with zirconium-89 has become a consistent tool in preclinical and clinical drug development and patient selection, primarily due to its advantageous physical properties that allow straightforward radiolabeling of antibodies (89Zr-immuno-PET). The extended half-life of 78.4 h permits flexibility with respect to the logistics
-
Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE EJNMMI Radiopharm. Chem. Pub Date : 2024-05-08 Asif Noor, Peter D. Roselt, Emily R. McGowan, Stan Poniger, Michael P. Wheatcroft, Paul S. Donnelly
Automated [89Zr]Zr-radiolabeling processes have the potential to streamline the production of [89Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [89Zr][Zr(ox)4]4− as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [89Zr]ZrCl4 as starting material gives better radiochemical yields at lower reaction temperatures. In this work
-
Bifunctional octadentate pseudopeptides as Zirconium-89 chelators for immuno-PET applications EJNMMI Radiopharm. Chem. Pub Date : 2024-05-06 Valentina Albanese, Chiara Roccatello, Salvatore Pacifico, Remo Guerrini, Delia Preti, Silvia Gentili, Matteo Tegoni, Maurizio Remelli, Denise Bellotti, Jonathan Amico, Giancarlo Gorgoni, Emiliano Cazzola
Positron emission tomography (PET) is a highly sensitive method that provides fine resolution images, useful in the field of clinical diagnostics. In this context, Zirconium-89 (89Zr)-based imaging agents have represented a great challenge in molecular imaging with immuno-PET, which employs antibodies (mAbs) as biological vectors. Indeed, immuno-PET requires radionuclides that can be attached to the
-
Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape EJNMMI Radiopharm. Chem. Pub Date : 2024-05-04 Raymond M. Reilly, Constantine J. Georgiou, Madeline K. Brown, Zhongli Cai
Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups. Gold nanoparticles were
-
99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications EJNMMI Radiopharm. Chem. Pub Date : 2024-05-02 Alessandra Boschi, Luca Urso, Licia Uccelli, Petra Martini, Luca Filippi
In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography
-
GMP production of [18F]FE-PE2I on a TRACERLab FX2 N synthesis module, a radiotracer for in vivo PET imaging of the dopamine transport EJNMMI Radiopharm. Chem. Pub Date : 2024-05-02 Mélodie Ferrat, Mohammad M. Moein, Carmen Cananau, Tetyana Tegnebratt, Paul Saliba, Fredrik Norman, Carsten Steiger, Klas Bratteby, Erik Samén, Kenneth Dahl, Thuy A. Tran
Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [18F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo
-
Advancing 6-bromo-7-[11C]methylpurine to clinical use: improved regioselective radiosynthesis, non-clinical toxicity data and human dosimetry estimates EJNMMI Radiopharm. Chem. Pub Date : 2024-04-29 Severin Mairinger, Matthias Jackwerth, Ondřej Soukup, Matthias Blaickner, Clemens Decristoforo, Lukas Nics, Jens Pahnke, Marcus Hacker, Markus Zeitlinger, Oliver Langer
6-Bromo-7-[11C]methylpurine ([11C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [11C]BMP afforded a mixture of 7- and 9-[11C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [11C]BMP, the
-
Small animal PET imaging with the 68Ga-labeled pH (low) insertion peptide-like peptide YJL-4 in a triple-negative breast cancer mouse model EJNMMI Radiopharm. Chem. Pub Date : 2024-04-27 YueHua Chen, ShuangShuang Song, YanQin Sun, FengYu Wu, GuangJie Yang, ZhenGuang Wang, MingMing Yu
The aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator
-
Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model EJNMMI Radiopharm. Chem. Pub Date : 2024-04-18 Anna Durinova, Lucie Smutna, Pavel Barta, Rajamanikkam Kamaraj, Tomas Smutny, Bernhard Schmierer, Petr Pavek, Frantisek Trejtnar
Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of 68Ga-
-
Automated radiolabelling of [68Ga]Ga-PSMA-11 (gallium (68Ga)-gozetotide) using the Locametz® kit and two generators EJNMMI Radiopharm. Chem. Pub Date : 2024-04-17 Elke A. van Brandwijk, Else A. Aalbersberg, Arman S. Hosseini, Alwin D. R. Huitema, Jeroen J. M. A. Hendrikx
Steps have been taken by pharmaceutical companies to obtain marketing authorisation of PSMA ligands in the European Union. Since December 2022, Locametz® (PSMA-11, gozetotide) is licensed as kit for manual radiolabelling with gallium-68 and commercially available since mid-2023. The Summary of Product Characteristic (SmPC) describes manual radiolabelling with a maximum activity after radiolabelling
-
Comparison of approaches for increasing affinity of affibody molecules for imaging of B7-H3: dimerization and affinity maturation EJNMMI Radiopharm. Chem. Pub Date : 2024-04-16 Maryam Oroujeni, Matilda Carlqvist, Eva Ryer, Anna Orlova, Vladimir Tolmachev, Fredrik Y. Frejd
Radionuclide molecular imaging can be used to visualize the expression levels of molecular targets. Affibody molecules, small and high affinity non-immunoglobulin scaffold-based proteins, have demonstrated promising properties as targeting vectors for radionuclide tumour imaging of different molecular targets. B7-H3 (CD276), an immune checkpoint protein belonging to the B7 family, is overexpressed
-
Production of [211At]NaAt solution under GMP compliance for investigator-initiated clinical trial EJNMMI Radiopharm. Chem. Pub Date : 2024-04-15 Sadahiro Naka, Kazuhiro Ooe, Yoshifumi Shirakami, Kenta Kurimoto, Toshihiro Sakai, Kazuhiro Takahashi, Atsushi Toyoshima, Yang Wang, Hiromitsu Haba, Hiroki Kato, Noriyuki Tomiyama, Tadashi Watabe
The alpha emitter astatine-211 (211At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (131I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [211At]NaAt solution for intravenous administration under the good manufacturing practice guidelines
-
Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) EJNMMI Radiopharm. Chem. Pub Date : 2024-04-02 Aurélie Maisonial-Besset, David Kryza, Klaus Kopka, Sophie Levesque, Emmanuel Moreau, Barbara Wenzel, Jean-Michel Chezal
(S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic radiofluorination step. This work aims to develop a short, epimerization-free
-
Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects EJNMMI Radiopharm. Chem. Pub Date : 2024-04-02 Kun-Ju Lin, Shao-Yi Huang, Kuo-Lun Huang, Chin-Chang Huang, Ing-Tsung Hsiao
Tau pathology plays a crucial role in neurodegeneration diseases including Alzheimer’s disease (AD) and non-AD diseases such as progressive supranuclear palsy. Tau positron emission tomography (PET) is an in-vivo and non-invasive medical imaging technique for detecting and visualizing tau deposition within a human brain. In this work, we aim to investigate the biodistribution of the dosimetry in the
-
In vivo evaluation of tumor uptake and bio-distribution of 99mTc-labeled 1-thio-β-D-glucose and 5-thio-D-glucose in mice model EJNMMI Radiopharm. Chem. Pub Date : 2024-03-29 Fabian Muehlberg, Konrad Mohnike, Oliver S. Grosser, Maciej Pech, Juergen Goldschmidt, Karl-Heinz Smalla, Ricarda Seidensticker, Muzaffer Reha Ümütlü, Sinan Deniz, Jens Ricke, Ingo G. Steffen, Osman Öcal, Max Seidensticker
To investigate the capacity of 99mTc-labeled 1-thio-β-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and
-
Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections EJNMMI Radiopharm. Chem. Pub Date : 2024-03-26 Jyotsna Bhatt Mitra, Saurav Chatterjee, Anuj Kumar, Elina Khatoon, Ashok Chandak, Sutapa Rakshit, Anupam Bandyopadhyay, Archana Mukherjee
The urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting
-
In-target production of [11C]CH4 from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature EJNMMI Radiopharm. Chem. Pub Date : 2024-03-25 Semi Helin, Johan Rajander, Jussi Aromaa, Eveliina Arponen, Jatta S. Helin, Olof Solin
Production of [11C]CH4 from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [11C]CO2 to [11C]CH4 is a widely used roundabout method in 11C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [11C]CH4 is superior with respect to molar activity. We studied
-
Validation of a size exclusion method for concomitant purification and formulation of peptide radiopharmaceuticals EJNMMI Radiopharm. Chem. Pub Date : 2024-03-21 Sebastian Martin, Lennard Wendlinger, Alexandra Litvinenko, Radmila Faizova, Margret Schottelius
Both in clinical routine and in preclinical research, the established standard procedure for the final purification of radiometal-labeled peptide radiopharmaceuticals is cartridge-based reversed-phase (RP) solid phase extraction (SPE). It allows the rapid and quantitative separation of the radiolabeled peptide from hydrophilic impurities and easy integration into automated synthesis procedures. However
-
Correction: 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 : 2024-03-19 Ali Fele‑Paranj, Babak Saboury, Carlos Uribe, Arman Rahmim
Correction: EJNMMI Radiopharmacy and Chemistry (2024) 9:6 https://doi.org/10.1186/s41181-023-00236-w In the original publication of the article, inaccuracies were identified in Figures 3 and 7 due to an incorrect application of S values in the dose calculations. The S values, which should vary with tumor volume to accurately represent dose distribution, were mistakenly kept constant. Upon review, the
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
[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