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

Abstract

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. <b>Methods:</b> 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-[(6-¹⁸F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-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. <b>Results:</b> In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUV_max corrected for lean body mass (SUL_max) on images obtained after MSG administration in the parotids (24% ± 14%, <i>P</i> = 0.001), submandibular glands (35% ± 11%, <i>P</i> < 0.001), and kidneys (23% ± 26%, <i>P</i> = 0.014). Significant decreases were also observed in the lacrimal glands (49% ± 13%, <i>P</i> < 0.001), liver (15% ± 6%, <i>P</i> < 0.001), spleen (28% ± 13%, <i>P</i> = 0.001), and bowel (44% ± 13%, <i>P</i> < 0.001). A mildly lower blood pool SUL_mean was observed after MSG administration (decrease of 11% ± 13%, <i>P</i> = 0.021). However, significantly lower radiotracer uptake in terms of SUL_mean, SUL_peak, and SUL_max was observed in malignant lesions on scans performed after MSG administration than on the placebo studies (SUL_max median decrease, 33%; range, -1% to 75%; <i>P</i> < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. <b>Conclusion:</b> Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using ¹⁸F-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.