SNMMI 2026: Predictive Value of Baseline PSMA PET Imaging Biomarkers in 177Lu-DGUL Therapy: A Phase I/II trial Sub-analysis in mCRPC

(UroToday.com) The 2026 SNMMI annual meeting featured a genitourinary radiotherapeutics session and a presentation by Dr. Minseok Suh discussing a phase I/II trial in mCRPC assessing the predictive value of baseline PSMA PET imaging biomarkers in 177Lu-DGUL therapy. 177Lu-DGUL (Pocuvotide Satetraxetan) is a novel PSMA-targeting radioligand therapy utilizing a Glu-Urea-Lys derivative conjugated to a DOTA chelator, which has been shown to have lower uptake in normal organs and rapid clearance: 

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Following the prospective phase I/II study (NCT05547061), this sub-analysis aims to identify which baseline PSMA PET-derived imaging biomarkers best predict objective and biochemical responses in patients with mCRPC. The original trial design of the phase I/II study is highlighted in the following figure:

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Of the 91 patients enrolled and treated with 177Lu-DGUL in this phase II study, 78 patients were evaluable for treatment response and included in this imaging sub-analysis. The baseline characteristics for the 91 patient cohort is as follows in the table, representing a standard mCRCP cohort:

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Whole-body quantitative PET parameters were extracted from baseline scans, including uptake intensity (SUVmean, SUVmax), tumor volume-based metrics, and uptake heterogeneity assessed by the coefficient of variation. The predictive performance for objective response (RECIST v1.1) and biochemical response (PSA50) was assessed using logistic regression and ROC analysis. 

Within the evaluable group (n = 78), the confirmed objective response rate was 35.9%, and the disease control rate was 59.0%. PSA50 response rate was 66.7% and PSA80 response rate was 39.7%:

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The median PSA doubling time was not reached (95% CI 258 – not reached):

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Exploratory efficacy results showed that based on an updated analysis as of April 30, 2026, the median overall survival was 13.4 months (95% CI 11.8-17.6) and the median progression-free survival by RECIST v1.1 was 11.0 months (95% CI 8.3-14.3). Patients with lung and lymph node metastases demonstrated significantly higher objective response rates compared to those without, whereas liver metastases were a poor prognostic factor for radiographic progression-free survival:

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A dose-dependent improvement in clinical outcomes (objective response rate and radiographic progression-free survival) was observed with an increasing number of treatment cycles:

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SUVmean was the most robust and consistent predictor of response, demonstrating superior discriminative performance compared to tumor volume-based metrics for both objective response and PSA50 outcomes:

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SUVmean served as the significant prognostic determinant for prognostic outcomes, stratifying patients for both progression-free survival and overall survival:

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Dr. Suh concluded his presentation discussing a phase I/II trial in mCRPC assessing the predictive value of baseline PSMA PET imaging biomarkers in 177Lu-DGUL therapy with the following take-home points:

  • Primary efficacy outcome: The RECIST v1.1-based objective response rate was 35.9% in the evaluable group and 47.4% in the measurable group
  • Secondary efficacy results: Regarding the best PSA response, the proportions of patients achieving a PSA50 and PSA80 were 66.7% and 39.7%, respectively
  • Exploratory survival analysis: Based on the latest follow-up data, the median overall survival was 13.4 months (95% CI: 11.8–17.6), and the median radiographic progression-free survival was 11.0 months
  • Subgroup analysis: Subgroup analyses revealed that patients with lung or lymph node metastases exhibited a higher objective response rate, those with liver metastases experienced a shorter progression-free survival, and a greater number of treatment cycles was associated with better therapeutic response and survival outcomes.
  • Baseline PSMA PET analysis: Baseline PSMA PET analysis demonstrated that SUVmean was a robust predictor of therapeutic response and was significantly correlated with both progression-free survival and overall survival

Presented by: Minseok Suh, MD, PhD, Seoul National University Hospital, Seoul, Republic of Korea

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2026 Annual Meeting, Los Angeles, CA, Sat, May 30 – Tues, Jun 2, 2026.