Advances in PSMA Alpha Theragnostics

Alpha theranostics offer an attractive alternative form of therapy, which has best been investigated and documented with ²²⁵Ac-PSMA in patients with prostate cancer. Advantages offered by targeted alpha therapy include overcoming radiation resistance, oxygen independence, effecting double-stranded DNA breakages within the tumors with anticipated improved clinical outcomes and an acceptable side effect profile. The previous Seminars article on this topic, published in 2020, had to rely mostly on published case reports and small observational studies. In the last few years, however, several meta-analyses have emerged that evaluate the safety and efficacy of ²²⁵Ac-PSMA in prostate cancer patients, followed most recently by a multi-center retrospective study initiated by WARMTH. The findings of these publications, together with the exploration of TAT offered in clinical conditions other than as a last resort, is the focus of this updated overview. Unresolved clinical issues that remain, include the appropriate selection of patients that would benefit most from treatment with ²²⁵Ac-PSMA, treatment timing within the disease landscape, optimal dosing schedule, dosimetry, when and how to best use combination therapies and minimization and treatment of side effects, particularly that of xerostomia.