Synthesis, radiolabeling, and pre-clinical evaluation of [44Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer

Autor:	A Maiocchi, G Nagy, Z Baranyai, D Szikra, S Pandey, S Ghiani, R Stefania, György Trencsényi, I Hawala, A Vágner
Rok vydání:	2021
Předmět:	Biodistribution Chemistry Radiochemistry General Medicine Ligand (biochemistry) 030218 nuclear medicine & medical imaging 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo 030220 oncology & carcinogenesis LNCaP Peptide synthesis Radiology Nuclear Medicine and imaging Chelation Ex vivo Conjugate
Zdroj:	European Journal of Nuclear Medicine and Molecular Imaging. 48:2351-2362
ISSN:	1619-7089 1619-7070
Popis:	The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]− and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)]. B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5456791b2aacfa2aaa573bca0200bc67 https://doi.org/10.1007/s00259-020-05130-0 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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