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Abstract
Introduction. 225Ac-PSMA is actively used in Russia and worldwide; however, systematic safety data remain limited. Most published studies are retrospective or consist of individual case reports.
Aim. To evaluate the safety and determine the maximum tolerated injected activity of the radiopharmaceutical 225Ac-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC).
Materials and Methods. We conducted a phase I, single-center, open-label, non-randomized clinical trial using a 3 + 3 dose-escalation design. Three patients per cohort with mCRPC progressing after standard therapies received a single intravenous administration of 225Ac-PSMA-617 at activities of 6.0 ± 10 % MBq, 9.0 ± 10 % MBq, and 12.0 ± 10 % MBq, respectively. Following safety evaluation, three additional patients were enrolled at the 12 MBq dose level. Dose-limiting toxicity (DLT) was assessed during a 6-week observation period.
Results. A total of 140 adverse events (AEs) were recorded in all 12 patients (100 %), including 133 mild and 6 moderate AEs. One serious AE (SAE) was unrelated to treatment and did not constitute a DLT. No severe or life-threatening treatment-related AEs were observed. The most frequent drug-related AEs were lymphopenia (75 %), xerostomia (83.3 %), and leukopenia (66.7 %). Absorbed radiation doses to critical organs remained within commonly applied in radiotherapy dose constraints.
Conclusion. 225Ac-PSMA-617 demonstrated a favorable safety profile at doses of 6–12 MBq in patients with mCRPC. The maximum tolerated dose was not reached in any cohort, establishing 12 MBq as the recommended dose for phase II efficacy evaluation. Trial Registration: Registered in the Clinical Trials Permission Registry (No. 530, November 7, 2024).
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