Renal excretion of some prostate-specific membrane antigen (PSMA) ligands and consequently increased bladder activity can obscure locally relapsing prostate cancer lesions in PSMA PET/CT. Furthermore, additional late imaging in PSMA PET/CT provides a useful method to clarify uncertain findings. The aim of this retrospective study was to investigate a modified imaging protocol combining late additional imaging with hydration and forced diuresis in individuals undergoing additional late scanning for uncertain lesions or low prostate-specific antigen. Methods: We compared an older protocol with a newer one. In the old protocol, patients undergoing ⁶⁸Ga-PSMA-11 PET/CT were examined at 90 min after injection, with 1 L of oral hydration beginning at 30 min after injection and 20 mg of furosemide given intravenously at 1 h after injection, followed by additional late imaging at 2.5 h after injection without further preparation. In the new protocol, a second group received the same procedure as before, with an additional 0.5 L of oral hydration and 10 mg of furosemide intravenously 30 min before the late imaging. We examined 132 patients (76 with the old protocol and 56 with the new one) with respect to urinary bladder activity (SUV_mean), prostate cancer lesion uptake (SUV_max), and lesion contrast (ratio of tumor SUV_max to bladder SUV_mean for local relapses and ratio of tumor SUV_max to gluteal-muscle SUV_mean for nonlocal prostate cancer lesions). Results: Bladder activity was significantly greater for the old protocol in the late scans than for the new protocol (ratio of bladder activity at 2.5 h to bladder activity at 1.5 h, 2.33 ± 1.17 vs. 1.37 ± 0.50, P < 0.0001). Increased tumor SUV_max and contrast were seen at 2.5 h compared with 1.5 h (P < 0.0001 for old protocol; P = 0.02 for new protocol). Increased bladder activity for the old protocol resulted in decreased lesion-to-bladder contrast, which was not the case for the new protocol. Tumor-to-background ratios increased at late imaging for both protocols, but the increase was significantly lower for the new protocol. For the old protocol, comparing the 1.5-h to the 2.5-h acquisitions, 4 lesions in 4 patients (4/76 = 5.2% of the cohort) were visible at the postdiuresis 1.5-h acquisition but not at 2.5 h, having been obscured as a result of the higher bladder activity. In the new protocol, 2 of 56 (3.6%) patients had lesions visible only at late imaging, and 2 patients had lesions that could be better discriminated at late imaging. Conclusion: Although the combination of diuretics and hydration can be a useful method to increase the visualization and detectability of locally recurrent prostate cancer in standard ⁶⁸Ga-PSMA-11 PET/CT, their effects do not sufficiently continue into additional late imaging. Additional diuresis and hydration are recommended to improve the visibility, detection, and diagnostic certainty of local recurrences.

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