Early Injection of Furosemide Increases Detection Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT

Abstract

The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for ⁶⁸Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (⁶⁸Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of ⁶⁸Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for ⁶⁸Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively (P = 0.048). Median maximum SUVs (SUV_max) of organs with physiologic uptake of ⁶⁸Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for ⁶⁸Ga-PSMA-11 PET/CT. As intensity of ⁶⁸Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of ⁶⁸Ga-PSMA-11 seems unlikely.

Keywords: 68Ga-PSMA-11; PET; PET/CT; biochemical recurrence; forced diuresis; furosemide; local recurrence; prostate cancer; prostate specific membrane antigen.

Graphical abstract

FIGURE 1.

Comparison of number of patients judged positive (pos.), negative (neg.), or equivocal for LR in relation to PSA level, together with PET-positive rate of LRs in each subgroup (%). G1 (no furosemide, blue column); G2 (with furosemide, red column).

FIGURE 2.

Example of an equivocal finding in prostate fossa on ⁶⁸Ga-PSMA-11 PET/CT with maximum-intensity-projection (A), fused axial (B), fused coronal (C), and fused sagittal (D) images of a PC patient with BR after radical prostatectomy and salvage radiation therapy (PSA: 1.34 ng/mL), receiving no preparation before imaging. Intense focal uptake is present in midline at level of vesicourethral anastomosis (red arrow). Clear distinction between LR and urinary activity within urethra is not possible (SUV_max of focal uptake in midline: 10.3 and SUV_max of urinary bladder: 118.0).

FIGURE 3.

⁶⁸Ga-PSMA-11 PET/CT with maximum-intensity-projection (A), fused axial (B), fused coronal (C), and fused sagittal (D) images of a PC patient with BR after radical prostatectomy (PSA: 1.18 ng/mL), who received forced diuresis with 20 mg of furosemide simultaneously with radiotracer injection. Focal uptake of high intensity with SUV_max of 9.6 is present in area of vesicourethral anastomosis (red arrow) that can be clearly distinguished from adjacent urinary activity in bladder (SUV_max of 9.4), representing case consistent with LR. Malignant origin of finding was confirmed on subsequent MRI.