The impact of monosodium glutamate on ⁶⁸Ga-PSMA-11 biodistribution in men with prostate cancer: a prospective randomized, controlled, imaging study

Abstract

Background: The prostate-specific membrane antigen (PSMA) has been targeted for PET imaging and radioligand therapy (RLT) in patients with prostate cancer. Xerostomia is a common side effect of RLT due to high salivary gland uptake of PSMA-radioligands. Here we aimed to determine the impact of monosodium glutamate (MSG) administration on PSMA-radioligand biodistribution within healthy organs and tumor lesions by using ⁶⁸Ga-PSMA-11 PET imaging. Methods: 16 men with prostate cancer were randomized (1:1) into oral ingestion and oral topical application (‘swishing’) arms. Each subject underwent two ⁶⁸Ga-PSMA-11 PET/CT scans within 14 days under baseline and MSG conditions. Salivary glands and whole-body tumor lesions were segmented using qPSMA software. We quantified tracer uptake via mean and maximum standardized uptake values (SUVmean and SUV_max) and compared parameters within each patient. Results: For the oral ingestion arm, salivary gland SUVmean/max decreased on average from Control to MSG scan by 45±15% (P = 0.004) and 53±11% (p<0.001), respectively. Tumor lesions SUVmean/ max also decreased by 38% (IQR -67%, -33%) and -52% (IQR -70%, -49%), respectively (P = 0.018). Swishing had no significant effect on ⁶⁸Ga-PSMA-11 accumulation in normal organs or tumor lesions. Conclusion: Oral ingestion but not topical application of MSG reduced ⁶⁸Ga-PSMA-11 uptake in salivary glands. Tumor uptake also declined, therefore, the clinical application of MSG is unlikely to be useful in the framework of RLT.