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 (177Lu) and the alpha emitter (225Ac) and exhibits a high level of radiostability. Autoradiography
confirmed that 177Lu-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 177Lu-PSMA-617 (2517
± 499 h %ID/cm3 vs 575 ± 75 h %ID/cm3). 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.