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: 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.
Authors
- Mikhail A. Kalinin (ORCID: https://orcid.org/0000-0002-0056-4813)
- Anastasiia S. Garanina (ORCID: https://orcid.org/0000-0003-3442-9553)
- Sergey Z. Vatsadze (ORCID: https://orcid.org/0000-0001-7884-8579)
- Alexander N. Vaneev (ORCID: https://orcid.org/0000-0001-8201-8498)
- Stanislav A. Petrov (ORCID: https://orcid.org/0000-0002-6000-6100)
- Alexander S. Erofeev (ORCID: https://orcid.org/0000-0002-6631-821X)
- Elena Kimovna Beloglazkina (ORCID: https://orcid.org/0000-0001-6796-8241)
- Stepan Nikolaevich Kalmykov (ORCID: https://orcid.org/0000-0002-2396-4561)
- Aleksei E. Machulkin (ORCID: https://orcid.org/0000-0001-7975-0346)
- Anna B. Priselkova
- Алексей В. Медведько (ORCID: https://orcid.org/0000-0002-8731-6934)
- Bayirta V. Egorova (ORCID: https://orcid.org/0000-0002-2927-7359)
- Roman V. Timoshenko (ORCID: https://orcid.org/0009-0007-6459-6455)
- Maria D. Kraynova
Institutions
- National University of Science and Technology (RU)
- Peoples' Friendship University of Russia (RU)
- Lomonosov Moscow State University (RU)
- Frumkin Institute of Physical Chemistry and Electrochemistry Russian Academy of Sciences (RU)
- N.D. Zelinsky Institute of Organic Chemistry (RU)
Publication Details
- Journal
- Organics
- Published
- 2025-02-10
- DOI
- https://doi.org/10.3390/org6010007
- Citations
- 1
- Primary Topic
- Radiopharmaceutical Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.36
Funders
- Russian Science Foundation
- National University of Science and Technology