Reduction of ⁶⁸Ga-PSMA renal uptake with mannitol infusion: preliminary results

Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with ⁶⁸Ga or ¹⁷⁷Lu 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 of ⁶⁸Ga-PSMA.

Kidney uptake (SUVmax) was calculated in nine patients undergoing ⁶⁸Ga-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 after ⁶⁸Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after ⁶⁸Ga-PSMA administration (B-infusion).

In patients receiving the A-infusion, mean SUV_max increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUV_max decreased by 24.3% and 22.4% in the right and left kidney, respectively.

Our preliminary findings indicate that mannitol may play a role in reducing off-target ⁶⁸Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before ⁶⁸Ga-PSMA injection. These results warrant dosimetric studies in patients treated with ¹⁷⁷Lu-PSMA to find the best scheme for mannitol administration.