225Ac-PSMA-617 is the next generation of prostate cancer treatment following the therapeutic success of 177Lu-PSMA-617. In the first clinical trials, xerostomia, i.e. dryness of the mouth was the only observed side-effect.

By end of 2017, 80 patients had been treated with 225Ac-PSMA-617. A study published in July 2016 reported the first results with two specific patients. 68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq (3 µCi) activity of 225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. In both patient’s PSA levels have decreased from higher than 3,000 ng/mL (initial life-expectancy was below 4 months) to undetectable (below 0.1 ng/mL). At time of publication, follow up was 23 months post treatment. Post treatment follow up for some patients reaches now 4+ years.

A prospective early Phase I clinical trial was initiated in China in January 2020 with a drug called 225Ac-PSMA (It is not clear which form of PSMA Vector was used, but there is a high probability that this drug is the same PSMA-617 derivative). This study is expected to be completed by end of 2021.

More recent clinical data have shown very interesting results in the tandem therapy combining lower doses of 177Lu-PSMA-617 and 225Ac-PSMA-617.

Target/Mechanism: PSMA

Leading Emitter: beta electrons (β)