Synthesis of Bispidine-Based Prostate-Specific Membrane Antigen-Targeted Conjugate and Initial Investigations
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
Organics · pp. 7–7 · Published 10 Feb 2025
10.3390/org6010007Abstract
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: 1H and 13C 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 64Cu in mild conditions. In vitro studies of the labeled conjugate [64Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with 64Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with 64Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.
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