The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). 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. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [ 18 F]DCFPyl PET/CT imaging sessions were performed 3-7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two 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 ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P=0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P=0.014). 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 bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 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. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [ 18 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.

Background Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy. Methods This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [18F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients’ characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up. Results Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6–32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2–5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not. Conclusions This study suggests that RT or surgery based on [18F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes. Trial registration Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312

4022 Background: Somatostatin receptor imaging (SRI) is a standard of care for patients with GEPNETs. The additional value of concurrent 18F-FDG PET/CT (FDG PET) remains unclear. We reviewed a prospective functional imaging study to determine the utility of FDG PET in GEPNENs. Methods: PETNET is a prospective study in British Columbia, Canada, which provides all 68Ga-DOTA-TOC (DOTA PET) imaging in the province. Every patient receives a DOTA PET scan and an FDG PET within 30 days. PETNET enrolls all patients with an indication for SRI. Scans are ordered per treating physician discretion at any point in the disease course. This abstract focuses on the WD-GEPNEN population. Only the first dual functional imaging scans were analyzed and FDG was interpreted qualitatively (positive/negative). Results: From 04/2017-01/2023, 375 patients with NEN were enrolled, 165 (44%) with metastatic GEPNENs. Baseline characteristics are described. Median time between scans was 4 days (IQR 1-11). The proportion of patients with positive FDG PET at baseline increased with WHO grade. For patients with well differentiated G1 to G3 GEPNENs (N=161), overall survival was significantly lower with a positive FDG PET (HR: 4.22; 95%CI 1.61-11.02 p=0.001). FDG remained prognostic when G3 tumors were excluded (N=148) (HR 3.52; 95%CI 1.32-9.42 p= 0.007). When analyzing dual tracer PET imaging, patients with DOTA+/FDG- had reduced risk of dying in comparison with DOTA+/FDG+ (HR:0.26; 95%CI 0.09-0.67 p=0.01). After multivariate analysis, FDG positivity remained independently associated with reduced survival (HR 2.87; 95%CI 1.06-7.75 p=0.04) when controlling for grade of tumor and age. Conclusions: In this prospective cohort of metastatic GEPNENs, a positive FDG PET was significantly associated with reduced overall survival. These results provide additional evidence to support dual tracer functional imaging use in metastatic well differentiated GEPNEN’s. [Table: see text]