Bladder activity of different PSMA PET radioligands and impact of furosemide

Prostate-specific membrane antigen (PSMA) radioligands used for PET imaging of prostate cancer (PCa) have variable urinary excretion. The prostate bed region is an important site of disease localization where intense bladder activity may obscure lesion detection. We performed a comparative analysis of bladder activity across different PSMA radioligands and investigated the impact of furosemide administration on reducing bladder activity. We analyzed the PSMA PET/CT images of patients with PCa who were imaged with ⁶⁸Ga-PSMA-11 with/without 20 mg furosemide, ¹⁸F-PSMA-1007, ¹⁸F-DCFPyL, ¹⁸F-rhPSMA-7.3 with/without 20 mg furosemide. We determined and compared bladder volume and bladder activity level using mean and maximum standardized uptake values (SUV_mean and SUV_max) between PET scans obtained with the different PSMA radioligands using an ANOVA or Kruskal-Wallis test, as appropriate. We also determined the association between the bladder activity level versus bladder volume using Spearman correlation. 210 PSMA PET/CT studies were reviewed, including 50, 20, 20, 28, 42, and 50 completed with ¹⁸F-PSMA-1007 without furosemide, ¹⁸F-rhPSMA-7.3 without furosemide, ¹⁸F-rhPSMA-7.3 with furosemide, ⁶⁸Ga-PSMA-11 without furosemide, ⁶⁸Ga-PSMA-11 with furosemide, and ¹⁸F-DCFPyL without furosemide, respectively. The median bladder SUV_mean (range) without furosemide were: 1.75 (0.4-6.4) [¹⁸F-PSMA-1007], 10.00 (1.9-140.0) [¹⁸F-rhPSMA-7.3], 15.92 (2.0-106.0) [⁶⁸Ga-PSMA-11], and 25.7 (7.9-87.6) [¹⁸F-DCFPyL], (P<0.001). With 20 mg furosemide co-administered with the radiotracer, there was a significant decline in bladder activity level (median SUV_mean of 10.00 (1.9-140.0) to 2.95 (0.8-17.6) for ¹⁸F-rhPSMA-7.3 and 15.92 (2.0-106.0) to 10.21 (2.6-281.3) for ⁶⁸Ga-PSMA-11 and a significant increase in bladder volume, P<0.05. There was a significant negative correlation between bladder SUV_max and bladder volume for the entire cohort, P=0.008, r=-0.181. There is variation in the bladder radioactivity between the different PSMA radioligands for PCa PET imaging, with ¹⁸F-PSMA-1007 demonstrating the lowest, ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL the highest, and ¹⁸F-rhPSMA-7.3 intermediate bladder activity level. Administration of 20 mg furosemide produces a significant reduction in bladder activity and an increase in bladder volume. With 20 mg furosemide, bladder activity of ¹⁸F-rhPSMA-7.3 approaches that of ¹⁸F-PSMA-1007.