The Effects of Monosodium Glutamate on PSMA Radiotracer Uptake in Men with Recurrent Prostate Cancer: A Prospective, Randomized, Double-Blind, Placebo-Controlled Intraindividual Imaging Study.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer. However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA-targeting radiotracer. This prospective, double-blind, placebo-controlled study enrolled 10 patients with biochemically recurrent prostate cancer. Each subject served as his own control. PET/CT imaging sessions using 2-(3-{1-carboxy-5-[(6-F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) were performed 3-7 d apart, after oral administration of either 12.7 g of MSG or placebo. Data from the 2 sets of images were analyzed by placing regions of interest on lacrimal, parotid, and submandibular glands; left ventricle; liver; spleen; kidneys; bowel; urinary bladder; gluteus muscle; and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the region-of-interest data. In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUV corrected for lean body mass (SUL) on images obtained after MSG administration in the parotids (24% ± 14%, = 0.001), submandibular glands (35% ± 11%, < 0.001), and kidneys (23% ± 26%, = 0.014). Significant decreases were also observed in the lacrimal glands (49% ± 13%, < 0.001), liver (15% ± 6%, < 0.001), spleen (28% ± 13%, = 0.001), and bowel (44% ± 13%, < 0.001). A mildly lower blood pool SUL was observed after MSG administration (decrease of 11% ± 13%, = 0.021). However, significantly lower radiotracer uptake in terms of SUL, SUL, and SUL was observed in malignant lesions on scans performed after MSG administration than on the placebo studies (SUL median decrease, 33%; range, -1% to 75%; < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using F-DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.