Tower Urology Medical Group

32 Background: PET-based radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have become the mainstay of prostate cancer imaging; however, high urinary radioactivity from these primarily renally cleared compounds may obscure tumors in the prostate and peri-ureteric regions. We conducted the first intra-patient comparator study to assess the urinary radioactivity of two 18 F-labelled PSMA-PET radiopharmaceuticals, 18 F-piflufolastat and 18 F-flotufolastat. Methods: This multicenter, prospective, intra-patient comparator study (NCT06604442) enrolled men ≥ 18 years with low PSA (≤ 0.5 ng/mL) biochemical recurrence of prostate cancer ≥ 6 months after radical prostatectomy with undetectable PSA post-surgery, scheduled for a standard-of-care (SoC) 18 F-piflufolastat PET. Patients had a SoC PET/CT after IV 18 F-piflufolastat (target dose 333 MBq), and a second PET/CT 1–10 days later after IV 18 F-flotufolastat (target dose 296 MBq), both scans started approximately 60 min after administration and used the same scanner. The primary endpoint was the difference in urinary bladder radioactivity (mean standardized uptake value [SUV mean ]) between 18 F-piflufolastat PET and 18 F-flotufolastat PET. Secondary endpoints included patient and region-level detection rates (DR) for each radiopharmaceutical. Images were interpreted by two blinded central readers, with a third to resolve disagreements, allowing majority read results. Results: Between Oct 2024 and Jun 2025, 55 patients (mean PSA, 0.28 [range 0.09–0.50] ng/mL) were included in the primary efficacy analysis. Median bladder SUV mean was significantly higher with 18 F-piflufolastat (29.0; interquartile range [IQR], 18.9–40.8) than 18 F-flotufolastat (10.9; IQR, 6.0–18.5) with a median difference of 15.1 (IQR, 8.5–27.0; p<0.001 [Wilcoxon signed-rank test]). The patient-level DR was 27.3% (15/55) for 18 F-piflufolastat and 45.5% (25/55) for 18 F-flotufolastat (majority read). Among the 21 patients with very low PSA levels (≤ 0.2 ng/mL), 38.1% had a positive 18 F-piflufolastat scan compared with 52.4% for 18 F-flotufolastat scans (majority read). Regional and sub-regional DRs are shown in the table. Conclusions: In this intra-patient study, 18 F-flotufolastat showed significantly lower urinary radioactivity, and a higher overall DR than 18 F-piflufolastat indicating it may offer improved image assessment in regions close to the bladder. Clinical trial information: NCT06604442 . Region 18 F-Piflufolastat DR* n (%)N=55 18 F-Flotufolastat DR*n (%)N=55 Prostate bed 6 (10.9) 10 (18.2) Vesicourethral anastomosis 1 (1.8) 4 (7.3) Retrovesical 2 (3.6) 2 (3.6) Remnant seminal vesicles/ lateral surgical margin 2 (3.6) 4 (7.3) Pelvic lymph nodes 8 (14.5) 9 (16.4) Majority read. *≥ 1 PET positive lesion.

5102 Background: Accurate staging of recurrent prostate cancer (PC) is essential to inform the best treatment strategy. 64 Cu-SAR-bisPSMA may offer several advantages over the currently approved PSMA positron emission tomography (PET) agents due to its bivalent structure (SAR-bisPSMA) and longer half-life of 64 Cu (12.7h vs. <2h for 18 F and 68 Ga), as previously reported (2-3x higher tumor uptake and detection of additional PC lesions vs. approved PSMA PET agents). Methods: This was a Phase 1/2 study assessing the safety/efficacy of 64 Cu-SAR-bisPSMA (200 MBq) in PC patients with biochemical recurrence (BCR) and negative/equivocal standard of care (SOC) imaging (NCT05249127). PET/computed tomography (CT) imaging was performed on Day 0 and Day 1 (1-4h and 24±6h post-dose, respectively) and interpreted by 3 blinded central readers. PET/CT results were assessed against a composite Reference Standard (histopathology, SOC imaging [interpreted by 2 readers], prostate specific antigen response post-focal therapy). Efficacy endpoints included detection rate (DR; % participants with a positive scan out of all scanned participants) and correct detection rate (CDR; % participants with a true positive scan out of all scanned participants with at least one evaluable Reference Standard). Results: Fifty-two participants were enrolled (50 had 64 Cu-SAR-bisPSMA PET results); 39 and 30 had follow-up SOC imaging by Day 90 and by Day 180, respectively, and 9 had histopathology. 64 Cu-SAR-bisPSMA DR range across readers on Day 0 was 44–58% (95% confidence interval [CI]: 30–71.8), increasing on Day 1 to 58–80% (95% CI: 43.2–90). DR on follow-up SOC imaging by Day 90 ranged from 15-31% and 7-10% by Day 180. CDR as assessed against the composite Reference Standard on Day 0 was 19.0–26.2% (95% CI: 8.6; 42.0), increasing to 26.2–33.3% (95% CI: 13.9; 49.5) on Day 1. CDR was considerably higher when using histopathology as the Reference Standard (44.4–55.6% and 55.6–77.8% for Day 0 and Day 1, respectively), than SOC imaging (10.3–20.5% and 23.1%–25.6% for Day 0 and Day 1, respectively). Conclusions: 64 Cu-SAR-bisPSMA is effective in detecting PC in BCR of PC, with lesions identified in up to 80% of participants with negative/equivocal baseline SOC imaging. CDR was considerably higher when using the gold standard of histopathology to verify 64 Cu-SAR-bisPSMA PET lesions vs SOC imaging, which highlights the limitations of using less sensitive methods to verify the 64 Cu-SAR-bisPSMA PET findings. These results have important clinical implications, as the identification of lesions in BCR patients can inform different treatment pathways. Clinical trial information: NCT05249127 .

TPS346 Background: Between 20-40% of patients with prostate cancer (PC) will relapse within 10 years of their primary PC treatment, as identified through rising prostate-specific antigen (PSA) levels. Early diagnosis of biochemical recurrence (BCR) with accurate staging is essential to informing optimal treatment decision-making. Approximately 20% of biochemically recurrent PC patients show low or no PSMA expression on prostate-specific membrane antigen (PSMA)-targeted PET. Consequently, these patients are unlikely to benefit from PSMA-targeted agents and represent a significant unmet need for both imaging and therapy. The Gastrin Releasing Peptide receptor (GRPr) is a transmembrane G-protein coupled receptor that is upregulated in many human cancers, including PC. 64Cu-SAR-BBN, a GRPr-targeting agent, uses a radioactive form of copper, copper-64 (64Cu), to image cancers using PET. Initial clinical data have shown that 64Cu-SAR-BBN was able to detect lesions in 32% (8/25) of patients with BCR of PC and negative/equivocal PSMA PET. Methods: SABRE is a phase II, single arm, non-randomized, open-label study of 64Cu-SAR-BBN administered to patients with BCR of PC following definitive therapy. Key eligibility criteria include confirmed adenocarcinoma of the prostate, recurrence of PC based on rising PSA after definitive therapy and negative or equivocal findings for PC on an approved PSMA PET. Approximately 50 patients will be enrolled. The objectives are to assess the safety of 64Cu-SAR-BBN (200 MBq), and its ability to detect recurrent PC when traditional PSMA PET is not informative. Patients will complete a PET/CT on the same day (1 to 4 hours) and the next day (24 ±6 hours) post-dose. We hypothesize that delayed imaging may allow the detection of additional lesions compared to the scan performed on the same day of the administration of the product. The safety endpoint includes the incidence and severity of treatment-emergent adverse events and serious adverse events following the administration of 64Cu-SAR-BBN. Efficacy endpoints include correct detection rate (participant level) and positive predictive value (at participant and region level) at each scan timepoint independently. The 64Cu-SAR-BBN PET/CT scans will be assessed centrally by 3 independent, blinded readers. Each reader will evaluate the scans for the presence of pathological 64Cu-SAR-BBN uptake in the prostate bed/gland, pelvic lymph nodes (LN), extra pelvic LN, visceral/soft tissue and bone regions. Patients will be followed for up to 180 days to verify the findings. The 64Cu-SAR-BBN PET/CT results will then be assessed against a composite Reference Standard (histopathology, conventional imaging, and/or PSA levels) determined by an independent, blinded, central expert panel. 50% recruitment was reached on July 24, 2023. Clinical trial information: NCT05407311 .