The effects of monosodium glutamate on PSMA radiotracer uptake in men with recurrent prostate cancer: a prospective, randomized, double-blind, placebo-controlled intra-individual imaging study.

Objectives: 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 prospective study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer.

Methods: Ten patients with prostate cancer and biochemical recurrence post radical prostatectomy/curative intent radiotherapy were enrolled. The study was performed using a double-blind, placebo-controlled method, where each subject served as his own control. Two ¹⁸F-DCFPyl PET/CT imaging sessions were performed 3 - 7 days apart, following oral administration of either 12.7 g of MSG or placebo, 30 minutes prior to radiotracer injection. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle blood pool, liver, spleen, kidneys, colon, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Vital signs were measured and adverse events recorded for both scans.

Results: A total of 142 pathological lesions along with normal tissues were analyzed in 10 patients on both control and MSG ¹⁸F-DCFPyL PET/CT images. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values (SULmax) corrected for lean body mass on images obtained following MSG administration in the parotids (24 ± 14%, P value=0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P=0.014). On post-hoc analysis, significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P=0.001) and colon (44 ± 13%, P<0.001). Mildly lower blood pool mean standardized uptake value (SULmean) was observed after MSG administration (11 ± 13%, P=0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration.

Conclusions: 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 also caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

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