Synthesis of Bispidine-Based Prostate-Specific Membrane Antigen-Targeted Conjugate and Initial Investigations

Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: <...

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Main Authors: Aleksei E. Machulkin, Stanislav A. Petrov, Maria D. Kraynova, Anastasiia S. Garanina, Bayirta V. Egorova, Roman V. Timoshenko, Alexander N. Vaneev, Alexander S. Erofeev, Anna B. Priselkova, Mikhail A. Kalinin, Aleksei V. Medved′ko, Stepan N. Kalmykov, Elena K. Beloglazkina, Sergey Z. Vatsadze
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Organics
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Online Access:https://www.mdpi.com/2673-401X/6/1/7
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Summary:Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: <sup>1</sup>H and <sup>13</sup>C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by <sup>64</sup>Cu in mild conditions. In vitro studies of the labeled conjugate [<sup>64</sup>Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [<sup>64</sup>Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with <sup>64</sup>Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with <sup>64</sup>Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with <sup>64</sup>Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.
ISSN:2673-401X