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Meeting abstracts from the 21st European Symposium on Radiopharmacy and Radiopharmaceuticals EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-09-18
Alexandra I. Fonseca1, Sara Almeida1, José Sereno2, Hugo Ferreira3,4, Ivanna Hrynchak1, Célia Gomes3,4, Francisco Alves2,5, Antero Abrunhosa2 1ICNAS Pharma, Ed. ICNAS, Polo das Ciências da Saúde, University of Coimbra, Coimbra, Portugal. 2CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal. 3Faculty of Medicine, Coimbra Institute for Clinical and Biomedical
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Highlight selection of radiochemistry and radiopharmacy developments by editorial board EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-09-16 Peter JH. Scott, Ivan Penuelas, Ana Rey, Silvio Aime, Pillai M.R. Ambikalmajan, Ines Farinha Antunes, Frederik Cleeren, Zhaofei Liu, Beverley Ellis, Maryke Kahts, Fany Pricile Ekoume, Ivis F. Chaple, Emerson Bernardes, Martin Behe, Ya-Yao Huang, Renata Mikolajczak, Shozo Furumoto, Amal Elrefaei, Klaus Kopka
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 19 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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GMP-compliant automated radiosynthesis of [18F] SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2 A (SV2A) EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-09-10 Lijuan Chen, Xiaochen Li, Yao Ge, Huiqiang Li, Ruili Li, Xiaosheng Song, Jianfei Liang, Weifeng Zhang, Xiaona Li, Xiaoqi Wang, Yunjuan Wang, Yaping Wu, Yan Bai, Meiyun Wang
A novel positron emission tomography (PET) imaging tracer, [18F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we’ve automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [18F] SynVesT-1 boosting
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Radiopharmaceutical small-scale preparation in Europe: will we be able to harmonize the situation? EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-09-05 Estrella Moya, Celia Cerrato, Luis Miguel Bedoya, José Antonio Guerra
Radiopharmaceuticals have been considered a special group of medicines in Europe since 1989. The use of radiopharmaceuticals that have marketing authorization should always be the first option in clinical use, however due to their special properties the availability of approved radiopharmaceuticals is limited. For this reason, they can be produced on a small scale outside the marketing authorization
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DESI-TQ-MS imaging for ex vivo brain biodistribution assessment: evaluation of LBT-999, a ligand of the dopamine transporter (DAT) EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-27 Laurent Galineau, Emmanuelle Claude, Zuhal Gulhan, Sylvie Bodard, Sophie Sérrière, Camille Dupuy, Jérémy Monteiro, Adeline Oury, Priscila Bertevello, Gabrielle Chicheri, Johnny Vercouillie, Lydie Nadal-Desbarats, Sylvie Chalon, Antoine Lefèvre, Patrick Emond
Selection of the most promising radiotracer candidates for radiolabeling is a difficult step in the development of radiotracer pharmaceuticals, especially for the brain. Mass spectrometry (MS) is an alternative to study ex vivo the characteristics of candidates, but most MS studies are complicated by the pharmacologic doses injected and the dissection of regions to study candidate biodistribution.
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Developments in radionanotheranostic strategies for precision diagnosis and treatment of prostate cancer EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-24 Jubilee Andrew, Amanda-Lee Ezra-Manicum, Bwalya Angel Witika
Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). Hence, there is a need for novel PCa agents
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Radiosynthesis and preclinical evaluation of a 68Ga-labeled tetrahydroisoquinoline-based ligand for PET imaging of C-X-C chemokine receptor type 4 in an animal model of glioblastoma EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-20 Piyapan Suwattananuruk, Sukanya Yaset, Chanisa Chotipanich, Angel Moldes-Anaya, Rune Sundset, Rodrigo Berzaghi, Stine Figenschau, Sandra Claes, Dominique Schols, Pornchai Rojsitthisak, Mathias Kranz, Opa Vajragupta
This study aimed to develop a novel positron emission tomography (PET) tracer, [68Ga]Ga-TD-01, for CXCR4 imaging. To achieve this goal, the molecular scaffold of TIQ15 was tuned by conjugation with the DOTA chelator to make it suitable for 68Ga radiolabeling. A bifunctional chelator was prepared by conjugating the amine group of TIQ15 with p-NCS-Bz-DOTA, yielding TD-01, with a high yield (68.92%).
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Scalability study on [133La]LaCl3 production with a focus on potential clinical applications EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-15 Santiago Andrés Brühlmann, Martin Walther, Magdalena Kerstin Blei, Constantin Mamat, Klaus Kopka, Robert Freudenberg, Martin Kreller
In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter 225Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide
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109Pd/109mAg in-vivo generator in the form of nanoparticles for combined β- - Auger electron therapy of hepatocellular carcinoma EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-13 Nasrin Abbasi Gharibkandi, Kamil Wawrowicz, Rafał Walczak, Agnieszka Majkowska-Pilip, Mateusz Wierzbicki, Aleksander Bilewicz
Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when
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Development of caspase-3-selective activity-based probes for PET imaging of apoptosis EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-08 Louis Lauwerys, Lucas Beroske, Angelo Solania, Christel Vangestel, Alan Miranda, Nele Van Giel, Karuna Adhikari, Anne-Marie Lambeir, Leonie wyffels, Dennis Wolan, Pieter Van der Veken, Filipe Elvas
The cysteine-aspartic acid protease caspase-3 is recognized as the main executioner of apoptosis in cells responding to specific extrinsic and intrinsic stimuli. Caspase-3 represents an interesting biomarker to evaluate treatment response, as many cancer therapies exert their effect by inducing tumour cell death. Previously developed caspase-3 PET tracers were unable to reach routine clinical use due
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Cyclotron production of manganese-52: a promising avenue for multimodal PET/MRI imaging EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-08-02 Francesca Porto, Sara Cisternino, Emiliano Cazzola, Giorgia Speltri, Liliana Mou, Alessandra Boschi, Lorenza Marvelli, Giovanni Di Domenico, Antonella Pagnoni, Lucia De Dominicis, Irene Calliari, Claudio Gennari, Licia Uccelli, Gaia Pupillo, Giancarlo Gorgoni, Juan Esposito, Petra Martini
The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) holds promise for advancing diagnostic imaging capabilities. The METRICS project aims to develop cyclotron-driven production of 52Mn for PET/MRI imaging. Using the 52Cr(p,n)52Mn reaction, we designed chromium metal targets via Spark Plasma Sintering and developed a separation procedure for isolating 52Mn. Labeling
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The development of 177Lu-DOTA-CC-PSMA following a unified “Click Chemistry” protocol of synthesizing metal nuclide-conjugated radiopharmaceuticals EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-07-31 Xiaobei Zheng, Shuai Xue, Zhongqi Zhao, Shuxin Jin, Shuhua He, Lina Jia, Zheng Li, Christian Vanhove, Filip De Vos, Zijun Kuang, Tiantian Wang, Sara Neyt, Lan Zhang, Xiao Li
Currently, the synthesis pathway of metal nuclide-labeled radiopharmaceuticals is mainly divided into two steps: first, connecting the chelator with the target molecule, and second, labeling the metal nuclide to the chelator. However, the second step of the reaction to label the metal nuclide requires high temperature (90–100 °C), which tends to denature and inactivate the target molecule, leading
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In vitro and in vivo analyses of eFAP: a novel FAP-targeting small molecule for radionuclide theranostics and other oncological interventions EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-07-29 Circe D. van der Heide, Hanyue Ma, Mark W.H. Hoorens, Joana D. Campeiro, Debra C. Stuurman, Corrina M.A. de Ridder, Yann Seimbille, Simone U. Dalm
Fibroblast activation protein (FAP), a transmembrane serine protease overexpressed by cancer-associated fibroblasts in the tumor stroma, is an interesting biomarker for targeted radionuclide theranostics. FAP-targeting radiotracers have demonstrated to be superior to [18F]FDG PET/CT in various solid cancers. However, these radiotracers have suboptimal tumor retention for targeted radionuclide therapy
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Generic semi-automated radiofluorination strategy for single domain antibodies: [18F]FB-labelled single domain antibodies for PET imaging of fibroblast activation protein-α or folate receptor-α overexpression in cancer EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-07-24 Herlinde Dierick, Laurent Navarro, Hannelore Ceuppens, Thomas Ertveldt, Ana Rita Pombo Antunes, Marleen Keyaerts, Nick Devoogdt, Karine Breckpot, Matthias D’Huyvetter, Tony Lahoutte, Vicky Caveliers, Jessica Bridoux
Radiofluorination of single domain antibodies (sdAbs) via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) has shown to be a promising strategy in the development of sdAb-based PET tracers. While automation of the prosthetic group (PG) [18F]SFB production, has been successfully reported, no practical method for large scale sdAb labelling has been reported. Therefore, we optimized and automated the PG
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Process validation and preclinical development of a new PET cerebral blood flow tracer [11C]MMP for initial clinical trials EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-07-23 Jun Toyohara, Tetsuro Tago, Muneyuki Sakata
2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is commonly used for diagnosis of dementia because brain glucose metabolism reflects neuronal activity. However, as [18F]FDG is an analogue of glucose, accumulation of tracer in the brain is affected by plasma glucose levels. In contrast, cerebral blood flow (CBF) tracers are theoretically unaffected by plasma glucose levels and are therefore expected to be
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Preclinical evaluation of CXCR4 peptides for targeted radionuclide therapy in glioblastoma EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-07-15 Anthony Waked, Melissa Crabbé, Virginie Neirinckx, Sunay Rodriguez Pérez, Jasmien Wellens, Bernard Rogister, M. Abderrafi Benotmane, Koen Vermeulen
Glioblastoma (GBM), is the most fatal form of brain cancer, with a high tendency for recurrence despite combined treatments including surgery, radiotherapy, and chemotherapy with temozolomide. The C-X-C chemokine receptor 4 (CXCR4) plays an important role in tumour radioresistance and recurrence, and is considered as an interesting GBM target. TRT holds untapped potential for GBM treatment, with CXCR4-TRT
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cGMP compliant one-step, one-pot automated [18F]FBnTP production for clinical imaging of mitochondrial activity EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-27 Mai Lin, Cong-Dat Pham, Robert T. Ta, H. Charles Manning
4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic
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Automated radiosynthesis and preclinical evaluation of two new PSMA-617 derivatives radiolabelled via [18F]AlF2+ method EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-21 Marco Nicola Iannone, Silvia Valtorta, Stefano Stucchi, Stefano Altomonte, Elia Anna Turolla, Elisa Vino, Paolo Rainone, Valentina Zecca, Alessia Lo Dico, Marco Maspero, Mariangela Figini, Matteo Bellone, Samuele Ciceri, Diego Colombo, Clizia Chinello, Lisa Pagani, Rosa Maria Moresco, Sergio Todde, Patrizia Ferraboschi
In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be “PSMA-617”, and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory
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Recently developed radiopharmaceuticals for bacterial infection imaging EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-19 Maryke Kahts, Beverley Summers, Aadil Gutta, Wilfrid Pilloy, Thomas Ebenhan
Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship
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In vivo stable 211At-labeled prostate-specific membrane antigen-targeted tracer using a neopentyl glycol structure EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-17 Hiroyuki Suzuki, Kento Kannaka, Mizuki Hirayama, Tomoki Yamashita, Yuta Kaizuka, Ryota Kobayashi, Takahiro Yasuda, Kazuhiro Takahashi, Tomoya Uehara
Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211
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Trans-cyclooctene—a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-06 Karuna Adhikari, Maarten Vanermen, Gustavo Da Silva, Tim Van den Wyngaert, Koen Augustyns, Filipe Elvas
Trans-cyclooctenes (TCOs) are highly strained alkenes with remarkable reactivity towards tetrazines (Tzs) in inverse electron-demand Diels–Alder reactions. Since their discovery as bioorthogonal reaction partners, novel TCO derivatives have been developed to improve their reactivity, stability, and hydrophilicity, thus expanding their utility in diverse applications. TCOs have garnered significant
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Synthesis and evaluation of [18F]FBNAF, a STAT3-targeting probe, for PET imaging of tumor microenvironment EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-04 Anna Miyazaki, Yasukazu Kanai, Keita Wakamori, Serina Mizuguchi, Mikiya Futatsugi, Fuko Hirano, Naoya Kondo, Takashi Temma
Signal transducer and activator of transcription 3 (STAT3) is a protein that regulates cell proliferation and differentiation, and it is attracting attention as a new index for evaluating cancer pathophysiology, as its activation has been highly correlated with the development and growth of tumors. With the development of STAT3 inhibitors, the demand for imaging probes will intensify. Noninvasive STAT3
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Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-06-03 Tetsuro Tago, Jun Toyohara
Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation
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eTFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-05-22 Dylan Chapeau, Savanne Beekman, Maryana Handula, Erika Murce, Corrina de Ridder, Debra Stuurman, Yann Seimbille
Integrating radioactive and optical imaging techniques can facilitate the prognosis and surgical guidance for cancer patients. Using a single dual-labeled tracer ensures consistency in both imaging modalities. However, developing such molecule is challenging due to the need to preserve the biochemical properties of the tracer while introducing bulky labeling moieties. In our study, we designed a trifunctional
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In vitro and in vivo evaluation of a tetrazine-conjugated poly-L-lysine effector molecule labeled with astatine-211 EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-05-22 Chiara Timperanza, Holger Jensen, Ellinor Hansson, Tom Bäck, Sture Lindegren, Emma Aneheim
A significant challenge in cancer therapy lies in eradicating hidden disseminated tumor cells. Within Nuclear Medicine, Targeted Alpha Therapy is a promising approach for cancer treatment tackling disseminated cancer. As tumor size decreases, alpha-particles gain prominence due to their high Linear Energy Transfer (LET) and short path length. Among alpha-particle emitters, 211At stands out with its
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Highlight selection of radiochemistry and radiopharmacy developments by editorial board EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-05-16 Jun Toyohara, Danielle Vugts, Oliver C. Kiss, Sergio Todde, Xiang-Guo Li, Zhibo Liu, Zhi Yang, Nic Gillings, Emiliano Cazzola, Wiktor Szymanski, Nick van der Meulen, Raymond Reilly, Carlotta Taddei, Ralf Schirrmacher, Zijing Li, Yohannes Jorge Lagebo, Naoual Bentaleb, Marta de Souza Albernaz, Suzanne Lapi, Caterina Ramogida, Archana Mukherjee, Javier Ajenjo, Winnie Deuther-Conrad, Cécile Bourdeau
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 24 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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[68Ga]Ga-NODAGA-TriGalactan, a low molecular weight tracer for the non-invasive imaging of the functional liver reserve EJNMMI Radiopharm. Chem. (IF 4.4) Pub Date : 2024-05-15 Maximilian A. Zierke, Christine Rangger, Kimia Samadikhah, Marlene Panzer, Stefanie Dichtl, Nikolas Hörmann, Doris Wilflingseder, Andreas M. Schmid, Roland Haubner
Determination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan
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Good practices for 89Zr radiopharmaceutical production and quality control EJNMMI Radiopharm. Chem. (IF 4.4) 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
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Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE EJNMMI Radiopharm. Chem. (IF 4.4) 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
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Bifunctional octadentate pseudopeptides as Zirconium-89 chelators for immuno-PET applications EJNMMI Radiopharm. Chem. (IF 4.4) 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
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Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape EJNMMI Radiopharm. Chem. (IF 4.4) 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
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99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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Advancing 6-bromo-7-[11C]methylpurine to clinical use: improved regioselective radiosynthesis, non-clinical toxicity data and human dosimetry estimates EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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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. (IF 4.4) 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-
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Automated radiolabelling of [68Ga]Ga-PSMA-11 (gallium (68Ga)-gozetotide) using the Locametz® kit and two generators EJNMMI Radiopharm. Chem. (IF 4.4) 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
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Comparison of approaches for increasing affinity of affibody molecules for imaging of B7-H3: dimerization and affinity maturation EJNMMI Radiopharm. Chem. (IF 4.4) 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
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Production of [211At]NaAt solution under GMP compliance for investigator-initiated clinical trial EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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Validation of a size exclusion method for concomitant purification and formulation of peptide radiopharmaceuticals EJNMMI Radiopharm. Chem. (IF 4.4) 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
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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. (IF 4.4) 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
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Synthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET EJNMMI Radiopharm. Chem. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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. (IF 4.4) 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