Actinium-225 PSMA therapy is used in patients with metastatic castration-resistant prostate cancer when standard treatment options have proven ineffective or could not be applied.
Actinium-225 PSMA therapy, a rising star in theranostic medicine, offers a unique approach to detecting tumors and metastases and subsequently treating them with a specific drug. This method is an example of the transition to modern medical practices focused on each patient’s individual health condition. In prostate cancer, tumor tissues can be visualized with high sensitivity and specificity using Ga-68 PSMA PET/CT, followed by targeted treatment with Ac-225 PSMA. This theranostic approach is a novel method that has been successfully implemented with promising results.
In the context of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, phase 2 clinical trials conducted with the beta-emitting Lutetium-177 (Lu-177) have been successfully completed, and phase 3 trials have shown promising results. However, alpha-particle therapy targeted with Ac-225 PSMA has so far been evaluated through a few preclinical experiments, preliminary dosimetric studies, and retrospective observational studies. Initial clinical experiences indicate that Ac-225 PSMA achieves a PSA response of >50% in 63-70% of cases, a promising antitumor effect, a response duration of 10-15 months, and complete remission in approximately 10% of patients.
Due to a lack of comparative studies between Lu-177 PSMA and Ac-225 PSMA, it is not yet possible to definitively state the superiority of one agent over the other. However, Ac-225 PSMA, as an alpha-emitting therapy, has a shorter range compared to beta radiation, which provides potential advantages in specific clinical indications. For example, in cases with extensive bone marrow infiltration, Ac-225 PSMA can reduce radiation exposure to surrounding healthy cells. Another advantage is in the ablation of micrometastases in early-stage disease or patients who previously responded to treatment.
Additionally, there is preliminary evidence that Ac-225 PSMA is promising for patients with poor responses to Lu-177 PSMA or those with unfavorable prognostic biomarkers. Preclinical research has shown that alpha radiation may trigger a stronger abscopal effect compared to beta radiation, suggesting potential synergy with immunotherapy.
Ac-225 is an impressive radioactive element with a physical half-life of approximately 10 days, making it superior in terms of supply and labeling. Thanks to the emission of alpha particles, Ac-225 PSMA has a much higher biological potency compared to beta radiation. In simple terms, 8 MBq of Ac-225 PSMA can achieve the same in vivo biological effect as 7.4 GBq of Lu-177 PSMA, enabling treatment at 1,000 times lower radiation doses.
Today, de-escalation treatment protocols and Ac-225/Lu-177 PSMA “cocktail” tandem regimens are being applied to reduce the risk of developing xerostomia (dry mouth syndrome), thereby improving the tolerability of Ac-225 PSMA. This allows for effective treatment without compromising its antitumor efficacy.
