Abstract Background: Radiotheranostics is an emerging therapeutic strategy for metastatic castrationresistant prostate cancer (mCRPC). This study assessed the safety, dosimetry, and antitumor activity of the theranostic pair Ga-68-NGUL and Lu-177-DGUL in patients with mCRPC. Ga-68-NGUL is a novel PSMA-targeting PET tracer that lacks an amide bond, providing enhanced stability against proteolytic degradation. Lu-177-DGUL, a small molecule with high PSMA affinity, selectively targets prostate cancer cells and emits β-particles while sparing normal tissues. Methods: This open-label, single-arm, multicenter, Phase 1/2 trial assessed Ga-68-NGUL and Lu-177-DGUL. Phase 1 included dosimetry of Ga-68-NGUL in healthy volunteers and mCRPC patients, and evaluation of Lu-177-DGUL (150 and 200 mCi) to determine the maximum tolerated dose and organ dosimetry. In Phase 2, patients received Lu-177-DGUL at the recommended Phase 2 dose (RP2D) every 6 weeks for up to 6 cycles. Efficacy and safety were monitored throughout the study (ClinicalTrials. gov NCT05547061). Results: In Phase 1, Part A, Ga-68-NGUL dosimetry was analyzed in 6 subjects, showing the highest uptake in the bladder and kidney in both healthy volunteers and mCRPC patients. Lu-177-DGUL dosimetry was evaluated in 4 patients in the 150 mCi cohort, with the salivary glands receiving the highest absorbed dose, followed by the kidneys. No dose-limiting toxicities (DLTs) were observed in the 7 subjects in Phase 1, Part B, supporting 200 mCi as the RP2D. In Phase 2, 91 patients were treated with Lu-177-DGUL at 200 mCi. The primary endpoint, objective response rate (ORR) by RECIST 1. 1, was 35. 9% (7 complete responses and 21 partial responses). Key secondary endpoints supported these findings: ORR by PCWG-modified RECIST v1. 1 was 41. 0% (32 responders). PSA declines of ≥50% and ≥80% were observed in 66. 7% (52/78) and 39. 7% (31/78) of evaluable patients, respectively. Median PSA doubling time was not reached (95% CI, 258. 0-NA). Treatment-emergent adverse events occurring in ≥10% of patients included anemia (31. 9%) and dry mouth (13. 2%), and were generally manageable. Conclusions: Ga-68-NGUL and Lu-177-DGUL demonstrated a favorable safety profile, predictable dosimetry, and meaningful antitumor activity in mCRPC. Phase 1 confirmed acceptable organ radiation exposure, and Phase 2 showed clinically relevant responses with manageable toxicity at the RP2D. These findings support further evaluation of Lu-177-DGUL in comparative and laterphase trials. Citation Format: Seung-hwan Jeong, Cheol Kwak, Chang Wook Jeong, Sung Kyu Hong, Jae Lyun Lee, Eu Chang Hwang, Kyo Chul Koo, Keon Wook Kang, Gi Jeong Cheon, Minseok Suh. Safety, dosimetry, and RP2D determination of Ga-68-NGUL and Lu-177-DGUL (pocuvotide satetraxetan) in mCRPC: Results from a phase 1/2 study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT148.
Jeong et al. (Fri,) studied this question.