PET-Based Outcome Prediction in Patients with Prostate Cancer Scheduled for [²²⁵Ac]Ac-PSMA Radiopharmaceutical...

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Actinium-225-labeled prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT) shows promise for advanced metastatic castration-resistant prostate cancer.
• Predicting treatment response is crucial for optimizing patient selection and outcomes.

Purpose of the Study:

• To identify baseline predictors of outcome in patients undergoing [225Ac]Ac-PSMA-I&T RPT.
• To correlate pretherapeutic PSMA PET/CT imaging parameters with treatment response, progression-free survival (PFS), and overall survival (OS).

Main Methods:

• Retrospective analysis of 26 patients with metastatic castration-resistant prostate cancer receiving [225Ac]Ac-PSMA-I&T RPT.
• Segmentation of metastases on pretherapeutic [18F]F-PSMA-1007 PET/CT to assess SUVmax, SUVmean, PSMA tumor volume (PSMA-TV), and PSMA-total lesion quotient (PSMA-TLQ).
• Correlation of imaging parameters with PSA change, early progressive disease (PD), PFS, and OS.

Main Results:

• SUVmax and SUVmean correlated significantly with PSA change after 2 cycles of RPT.
• SUVmax and SUVmean predicted early PD. Patients with higher SUVmean had longer PFS (134 days vs. 39 days).
• PSMA-TLQ and PSMA-TV predicted OS. Patients with lower PSMA-TLQ had longer OS (375 days vs. 148 days).

Conclusions:

• Pretherapeutic [18F]F-PSMA-1007 PET/CT SUVmean is a strong predictor of early treatment response and PFS in patients receiving [225Ac]Ac-PSMA-I&T RPT.
• PSMA-TLQ is associated with OS, suggesting its utility in predicting long-term outcomes.
• PSMA PET-based quantification can optimize patient selection for targeted alpha-RPT.