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

• Published in: Organics (Basel) Vol. 6; no. 1; p. 7
• Main Authors: Machulkin, Aleksei E, Petrov, Stanislav A, Kraynova, Maria D, Garanina, Anastasiia S, Egorova, Bayirta V, Timoshenko, Roman V, Vaneev, Alexander N, Erofeev, Alexander S, Priselkova, Anna B, Kalinin, Mikhail A, Aleksei V Medved′ko, Kalmykov, Stepan N, Beloglazkina, Elena K, Vatsadze, Sergey Z
• Format: Journal Article
• Language: English
• Published: Leuven MDPI AG 01.03.2025
• Subjects: Antigens; bispidine bifunctional chelator; Chromatography; complexation; Copper; copper-64; delivery; Ligands; Nuclear medicine; Prostate cancer; PSMA; United States > US; Japan
• ISSN: 2673-401X; 2673-401X
• DOI: 10.3390/org6010007

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.