Emerging research suggests that the mean standardized uptake value (SUVmean) on baseline PSMA PET imaging may provide a key prognostic marker of progression-free survival (PFS) in patients treated with the (225Ac)Ac-PSMA-I&T radiopharmaceutical (RPT) for metastatic castration-resistant prostate cancer (mCRPC).
For the retrospective study, recently published in the Journal of Nuclear Medicine, researchers evaluated a variety of prostate-specific membrane antigen positron emission tomography (PSMA PET) for their prognostic capacity in predicting outcomes for 26 patients treated with the (225Ac)(Ac)-PSMA-I&T radiopharmaceutical for mCRPC.
The study authors found that patients with a high SUVmean (above the median of 6.8) had over a threefold higher duration of progression-free survival (134 days) in comparison to those with a low SUVmean (39 days).
The researchers also noted a correlation between SUVmean and progressive disease (PD). There was a higher SUVmean (7.66) in patients with no PD in contrast to those with PD (6.51), according to the study authors.
“These results might help the referring nuclear medicine specialist to consider (225Ac)Ac-PSMA RPT, in particular, in patients that have already experienced PD after conventional lutetium-labeled PSMA-targeted therapy,” suggested lead study author Liam Widjaja, M.D., who is affiliated with the Department of Nuclear Medicine at LMU University Hospital in Munich, Germany, and colleagues.
Three Key Takeaways
• Baseline PSMA PET SUVmean may help stratify responders to ²²⁵Ac-PSMA RPT. Patients with a higher SUVmean (>6.8) had more than a threefold longer progression-free survival (134 vs 39 days), suggesting SUVmean reflects treatment sensitivity in mCRPC.
• Higher SUVmean was associated with disease control. Patients without progressive disease had higher baseline SUVmean than those with progression, supporting SUVmean as a potential imaging biomarker for predicting treatment response.
• Tumor burden matters for overall survival, even if not PFS. While PSMA-total lesion quotient (PSMA-TLQ) was not prognostic for PFS, lower PSMA-TLQ (low tumor volume with high PSMA expression) was linked to substantially longer overall survival, highlighting complementary roles for intensity- and volume-based PSMA PET metrics.
While PSMA-total lesion quotient (PSMA-TLQ) was not prognostic for PFS, the researchers found that patients with a low PSMA-TLQ had a 2.5-fold higher duration of overall survival (OS) at 375 days in contrast to 148 days for those with a high PSMA-TLQ.
“A low PSMA-TLQ — indicating a low tumor volume combined with high PSMA expression — was associated with longer OS. As such, these preliminary results may lay the foundation for future studies using molecular imaging–derived biomarkers to identify patients that benefit from (225Ac)Ac-PSMA RPT,” posited Widjaja and colleagues.
(Editor’s note: For related content, see “Can PSMA PET Parameters Help Predict Toxicity and Outcomes in Patients Treated for mCRPC?,” “Top Five Prostate Cancer Imaging Content in 2025” and “Next-Generation PSMA Agent 225Ac-FL-020 Gets FDA Fast Track Designation for mCRPC.”)
In regard to study limitations, the authors acknowledged the small cohort size, four patients only having one treatment cycle of (225Ac)Ac-PSMA RPT and a lack of follow-up PET/CT imaging for eight patients who had PSA increases after treatment.
