{"entity": "publication", "iuid": "db898af5efd74111b3e58fc3e12a351b", "timestamp": "2026-09-30T01:02:27.693Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/db898af5efd74111b3e58fc3e12a351b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/db898af5efd74111b3e58fc3e12a351b"}}, "title": "Synthesis and preclinical evaluation of gastrin releasing peptide receptor antagonist [18F]MeTz-PEG2-RM26 for positron emission tomography.", "authors": [{"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P"}, {"family": "Lundmark", "given": "Fanny", "initials": "F"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Balestri", "given": "Lorenzo Jacopo Ilic", "initials": "LJI"}, {"family": "H\u00e5kansson", "given": "Esther Olaniran", "initials": "EO"}, {"family": "Obeid", "given": "Karim", "initials": "K"}, {"family": "Odell", "given": "Luke R", "initials": "LR"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "Eriksson", "given": "Jonas", "initials": "J"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2025-03-26", "journal": {"title": "EJNMMI Radiopharm Chem", "issn": "2365-421X", "volume": "10", "issue": "1", "pages": "14", "issn-l": null}, "abstract": "The gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of primary prostate cancer lesions, with persistent expression in lymph nodes and bone metastases, making it a legitimate molecular target for diagnostic imaging and staging. This study presents the synthesis and preclinical evaluation of [18F]MeTz-PEG2-RM26, a GRPR antagonist which utilises the Inverse Electron Demand Diels-Alder (IEDDA) reaction for 18F-labelling. This click-chemistry approach allows for site-specific incorporation of fluorine-18 under mild conditions, preserving the peptide's structural integrity and biological activity. Receptor specificity and affinity of [18F]MeTz-PEG2-RM26 were evaluated in vitro using GRPR-expressing PC-3 cells. Furthermore, the biodistribution profile of [18F]MeTz-PEG2-RM26 was assessed in NMRI mice and its tumour-targeting capability was investigated in mice bearing PC-3 xenografts.\n\nThe labelling of TCO-PEG2-RM26 precursor involved three steps: (1) synthesis of an 18F-labelled activated ester on a quaternary methyl ammonium (QMA) cartridge, (2) conjugation of the labelled ester to a tetrazine amine, and (3) attachment to TCO-PEG2-RM26 via an IEDDA click reaction. This production method of [18F]MeTz-PEG2-RM26 afforded a high apparent molar activity of 3.5-4.3 GBq/\u00b5mol and radiochemical purity exceeding 98%, with 43-70 MBq activity incorporation, while the entire synthesis was completed within 75 min. Both in vitro and in vivo studies confirmed the specific binding of [18F]MeTz-PEG2-RM26 to GRPR, with a significant reduction in activity uptake observed upon receptor saturation. The radioligand exhibited rapid blood clearance and minimal bone uptake, confirming the stability of the fluorine-carbon bond. However, high hepatic uptake (12-13% IA/g at 1 h post-injection) indicated predominant hepatobiliary excretion. Receptor-mediated uptake was observed in the tumours and pancreatic tissue, although the overall activity uptake in tumours was low, likely due to the rapid hepatobiliary clearance of [18F]MeTz-PEG2-RM26.\n\nThese findings demonstrate the effectiveness of the IEDDA click reaction for fluorine-18 labelling of GRPR-targeting PET tracers. Future studies should focus on increasing the hydrophilicity of the imaging probe to improve the targeting properties and biodistribution profile of the radioligand.", "doi": "10.1186/s41181-025-00336-9", "pmid": "40138074", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11947346"}, {"db": "pii", "key": "10.1186/s41181-025-00336-9"}], "notes": [], "created": "2026-09-23T13:18:34.421Z", "modified": "2026-09-23T13:18:34.470Z"}