Preclinical evaluation and preliminary human imaging of a novel 212Pb-based, PSMA-targeted radioligand, 212Pb-ADVC001, for prostate cancer treatment.
Radioligand therapy (RLT) is a targeted cancer therapy approach that utilizes a binder ligand (eg. peptide, small molecule etc.) to deliver radioactivity directly and specifically to tumor cells. To be effective, an RLT needs to 1) demonstrate target specificity, 2) show low or no accumulation in healthy tissues, and 3) accumulate and remain in the tumor long enough to have a therapeutic effect.
PSMA-targeted RLT with lutetium-177 (177Lu), a beta-emitter, has been clinically proven to be efficacious for the treatment of prostate cancer (PC). Although emerging clinical data indicate that better efficacy can be achieved by alpha-emitters, the toxicities associated with actinium-225 (225Ac) may limit its broad application especially in early lines of treatment. Lead-212 (212Pb), is a promising isotope for alpha therapy with a high linear energy transfer, a half-life of 10.6 hours, and a simple decay scheme. These properties promote efficient targeting of PSMA+ PC cells while limiting off-target toxicities. 212Pb-ADVC001 is a novel 212Pb-based PSMA-targeted RLT currently in Phase Ib/IIa clinical trial (NCT05720130) for patients with metastatic castration-resistant prostate cancer (mCRPC).
