Click Covalent-Targeted Radionuclide Therapy for Prostate Cancer
Targeted radionuclide therapy represents a promising therapeutic method for treating cancer. However, currently approved radioligands still require improvement in terms of tumor uptake and retention. This study employed molecular simulation to design a novel radioligand, designated PSMA-MAL-5, which covalently binds to the prostate-specific membrane antigen (PSMA). This ligand can be efficiently radiolabeled with the beta emitter (<sup>177</sup>Lu) and the alpha emitter (<sup>225</sup>Ac) and exhibits a high level of radiostability. Autoradiography confirmed that <sup>177</sup>Lu-PSMA-MAL-5 binds covalently to PSMA. In vivo experiments demonstrated that the radioligand can effectively target PSMA-positive tumors, with an area under the curve of tumor uptake higher than that observed for <sup>177</sup>Lu-PSMA-617 (2517 ± 499 h %ID/cm<sup>3</sup> vs 575 ± 75 h %ID/cm<sup>3</sup>). Tumor inhibition studies indicated that the radioligand exhibited a notable tumor inhibitory effect on tumor growth, showing promise as a tool for targeted radionuclide therapy of PSMA-positive prostate cancer.
Authors
- Guanglin Wang (ORCID: https://orcid.org/0000-0002-6463-119X)
- Wei Peng Yong (ORCID: https://orcid.org/0000-0003-4404-3777)
- Zhoudong Zhang (ORCID: https://orcid.org/0000-0001-5928-8828)
- Yu Qin (ORCID: https://orcid.org/0000-0002-1829-7864)
- Ran Zhu (ORCID: https://orcid.org/0000-0001-9351-4702)
- Huanqiu Li (ORCID: https://orcid.org/0000-0002-1487-6893)
- Xiaofei Qi (ORCID: https://orcid.org/0000-0003-0879-7344)
- Zhiyong Liu (ORCID: https://orcid.org/0000-0002-6409-3379)
- Zhihao Li (ORCID: https://orcid.org/0000-0002-1030-3924)
- Dong Wang (ORCID: https://orcid.org/0000-0002-6860-6864)
- Shu Zhang (ORCID: https://orcid.org/0000-0002-4380-1268)
- Yu‐Juan Zhang
- Jianguo Li (ORCID: https://orcid.org/0000-0001-9431-2950)
Institutions
- Target (United States) (US)
- Soochow University (TW)
- Soochow University (CN)
- Laboratoire de Radiopharmaceutiques Biocliniques (FR)
- National Institute for Radiological Protection (CN)
- Pharmaceutical Biotechnology (Czechia) (CZ)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c01515
- Citations
- 2
- Primary Topic
- Radiopharmaceutical Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 2.72
Funders
- National Natural Science Foundation of China
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- State Key Laboratory of Radiation Medicine and Protection