RT Journal Article SR Electronic T1 Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1624 OP 1631 DO 10.2967/jnumed.117.191395 VO 58 IS 10 A1 Clemens Kratochwil A1 Frank Bruchertseifer A1 Hendrik Rathke A1 Marcus Bronzel A1 Christos Apostolidis A1 Wilko Weichert A1 Uwe Haberkorn A1 Frederik L. Giesel A1 Alfred Morgenstern YR 2017 UL http://jnm.snmjournals.org/content/58/10/1624.abstract AB The aim of this study was to develop a treatment protocol for 225Ac-PSMA-617 α-radiation therapy in advanced-stage, metastatic castration-resistant prostate cancer patients with prostate-specific membrane antigen (PSMA)–positive tumor phenotype. Methods: A dosimetry estimate was calculated on the basis of time–activity curves derived from serially obtained 177Lu-PSMA-617 scans extrapolated to the physical half-life of 225Ac, assuming instant decay of unstable daughter nuclides. Salvage therapies empirically conducted with 50 (n = 4), 100 (n = 4), 150 (n = 2), and 200 kBq/kg (n = 4) of 225Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response. Eight of 14 patients received further cycles in either 2- or 4-mo intervals with identical or deescalated activities. Results: Dosimetry estimates for 1 MBq of 225Ac-PSMA-617 assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed of 99.4% α, 0.5% β, and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate-specific antigen decline was less than 4 mo, but if therapy was repeated every 2 mo patients experienced additive antitumor effects. Treatment activities of 50 kBq/kg were without toxicity but induced insufficient antitumor response in these high-tumor-burden patients. Remarkable antitumor activity by means of objective radiologic response or tumor marker decline was observed in 9 of 11 evaluable patients. Conclusion: For advanced-stage patients, a treatment activity of 100 kBq/kg of 225Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable trade-off between toxicity and biochemical response.