Despite an increase in the number of approved therapies for metastatic castration- resistant prostate cancer (mCRPC) in recent years, the survival advantage from most agents is measured in months, and the 5-year survival rate is approximately 30%.1
The radioligand therapy 177Lu-PSMA-617, which uses a beta-emitting isotope linked to a PSMA-targeting small molecule, has shown a median survival advantage in mCRPC of four months,2 underpinning the critical need for more effective treatments. Focus has shifted towards the use of alpha-emitting isotopes that deliver a more lethal payload.3 Unlike beta particles, alpha particles have a short range of tissue penetration (< 0.1 mm) and high linear energy transfer that induces double-stranded DNA breaks and high levels of cytotoxicity to target expressing cancer cells, irrespective of cell cycle or oxygenation state.
Herein we describe the ongoing clinical trial of [212Pb]Pb-ADVC001 – a novel PSMA- targeted radioligand labelled with the potent alpha-emitting isotope 212Pb.
