The effect of eating on the uptake of PSMA ligands in the salivary glands

Abstract

Rationale PSMA-directed therapy for metastatic prostate cancer is gaining adoption as a treatment option. However, accumulation of 177Lu/225Ac-PSMA in the salivary glands remains a problem, with risk of dose-limiting xerostomia and potentially severe effect on the quality of life. Gustatory stimulation is an approach that has commonly been used in radioactive iodine therapy to reduce accumulation in the salivary glands. However, based on theoretical differences in biodistribution, it was hypothesized that this could potentially lead to adverse increased toxicity for PSMA-ligand therapy. The primary objective of this work was to determine if gustatory stimulation by eating an assortment of sweet/fatty/acidic foods during the biodistribution phase of [18F]DCFPyl could result in a clinically relevant (> 30%) change in the uptake of the tracer in the salivary glands. Methods 10 patients who already received a whole-body [18F]DCFPyl PET/CT scan for evaluation of prostate cancer, underwent a repeat (intervention) PET/CT scan within a month of the first (control) scan. During the intervention scan, patients chose from an assortment of sweet/fatty/acidic foods, which they then chewed and swallowed for a period of time starting 1 min before tracer administration to 10 min thereafter. Data from both scans were analyzed by placing VOIs on the major salivary glands and segmenting them using relative thresholds. Results A slight increase in PSMA uptake in the parotid glands was observed on the intervention scan when compared to the baseline scan (+ 7.1% SULmean and + 9.2% SULmax, p < 0.05). No significant difference in PSMA uptake in the submandibular glands was seen. Conclusions Eating only slightly increases uptake of [18F]DCFPyl in the parotid glands. We nonetheless recommend refraining from gustatory stimulation during the administration and early biodistribution phase of radionuclide therapy with PSMA-ligands to reduce the risk of avoidable additional toxicity.

Radiolabeled PSMA Inhibitors

“…Uptake in the salivary glands is the dose-limiting factor during endoradiotherapy with small-molecule PSMA inhibitors, resulting in (partially reversible) xerostomia when applied with 177 Lu, and severe to persistent xerostomia when applied with 225 Ac [ 50 , 51 ]. The quality of life for patients can, therefore, be significantly impaired despite preventive strategies, e.g., injection of botulinum toxin, external cooling, or gustatory stimulation have been described [ 99 , 100 , 101 , 102 , 103 ]. The uptake mechanism of PSMA inhibitors in salivary glands has not been thoroughly investigated to date, a more comprehensive review concerning known mechanisms is described by Heynickx et al [ 103 ].…”