Reduction of68Ga-PSMA renal uptake with mannitol infusion: preliminary results

Purpose: Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with68Ga or177Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of68Ga-PSMA. Methods: Kidney uptake (SUVmax) was calculated in nine patients undergoing68Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after68Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after68Ga-PSMA administration (B-infusion). Results: In patients receiving the A-infusion, mean SUVmaxincreased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUVmaxdecreased by 24.3% and 22.4% in the right and left kidney, respectively. Conclusion: Our preliminary findings indicate that mannitol may play a role in reducing off-target68Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before68Ga-PSMA injection. These results warrant dosimetric studies in patients treated with177Lu-PSMA to find the best scheme for mannitol administration.