Quantitative and Qualitative Assessment of Urinary Activity of ¹⁸F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies

Purpose: To evaluate the impact of urinary activity on interpretation of ¹⁸F-flotufolastat (¹⁸F-rhPSMA-7.3) PET/CT, we conducted a post hoc qualitative and quantitative analysis of scans acquired in two phase 3 studies of ¹⁸F-flotufolastat. Procedures: Newly diagnosed or recurrent prostate cancer patients enrolled in LIGHTHOUSE (NCT04186819) or SPOTLIGHT (NCT04186845), respectively, underwent PET/CT 50–70 min after intravenous administration of 296 MBq ¹⁸F-flotufolastat. For the present analysis, 718 ¹⁸F-flotufolastat scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by three board-certified nuclear medicine physicians. Reader 1 performed a quantitative assessment (SUV_max and SUV_mean) of bladder activity in a circular region-of-interest over the maximum diameter of bladder activity in the transverse plane. All three readers qualitatively assessed the impact of any urinary activity in the bladder on image interpretation using a three-point scale (0 = no/minimal visible urinary activity, 1 = urinary activity visible but distinction between urine and disease possible and 2 = assessment inhibited by urinary activity) and the presence/absence of ureteric activity and halo artifacts. Results: In total, 712/718 scans were evaluable. Reasons for exclusion were cystectomy, renal failure, or urinary catheter in situ (n = 2 each). The median bladder SUV_max and SUV_mean were 17.1 and 12.5, respectively. By majority read, 682/712 (96%) patients had either no urinary activity (score = 0) or visible activity that could be distinguished from disease uptake (score = 1). In the minority of patients (24, 3.4%) where urinary activity did impact assessment (score = 2), the median bladder SUV_mean was higher (20.5) than those scored 0 (3.8) or 1 (14.0). Ureteric activity was absent in 401 (56%) patients. Halo artifacts were observed in only two (0.3%) patients (majority read). Conclusions: ¹⁸F-Flotufolastat urinary activity did not influence disease assessment for the majority of patients. While this study was not designed as a head-to-head comparison, the median bladder SUVs are lower than previously reported values for other renally cleared PSMA-PET radiopharmaceuticals.