64 Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates.

Autor: Kubeil M; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany., Neuber C; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany., Starke M; Universität Heidelberg, Anorganisch-Chemisches, Institut INF 270, 69120, Heidelberg, Germany., Arndt C; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany.; Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, Technische Universiät Dresden, 01307, Dresden, Germany., Rodrigues Loureiro L; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany., Hoffmann L; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany., Feldmann A; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany.; National Center for Tumor Diseases Dresden (NCT/UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany., Bachmann M; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany.; National Center for Tumor Diseases Dresden (NCT/UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany., Pietzsch J; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany.; Technische Universität Dresden, Faculty of Chemistry and Food Chemistry, School of Science, 01069, Dresden, Germany., Comba P; Universität Heidelberg, Anorganisch-Chemisches, Institut INF 270, 69120, Heidelberg, Germany.; Universität Heidelberg, Interdisciplinary Center for Scientific Computing, INF 205, 69120, Heidelberg, Germany., Stephan H; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Jun 06; Vol. 30 (32), pp. e202400366. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1002/chem.202400366
Abstrakt: Discussed are two picolinate appended bispidine ligands (3,7-diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis-pyridine derivative, which are all known to strongly bind Cu II . The radiopharmacological characterization of the two isomeric bispidine complexes includes quantitative labeling with 64 Cu II at ambient conditions with high radiochemical purities and yields (molar activities >200 MBq/nmol). Challenge experiments in presence of EDTA, cyclam, human serum and SOD demonstrate high stability and inertness of the 64 Cu-bispidine complexes. Biodistribution studies performed in Wistar rats indicate a rapid renal elimination for both 64 Cu-labeled chelates. The bispidine ligand with the picolinate group in N7 position was selected for further biological experiments, and its backbone was therefore substituted with a benzyl-NCS group at C9. Two tumor target modules (TMs), targeting prostate stem cell antigen (PSCA), overexpressed in prostate cancer, and the fibroblast activation protein (FAP) in fibrosarcoma, were selected for thiourea coupling with the NCS-functionalized ligand and lysine residues of TMs. Small animal PET experiments on tumor-bearing mice showed specific accumulation of the 64 Cu-labeled TMs in PSCA- and FAP-overexpressing tumors (standardized uptake value (SUV) for PC3: 2.7±0.6 and HT1080: 7.2±1.25) with almost no uptake in wild type tumors.
(© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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