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We aimed to explore whether the imaging of antiporter system x(C)(−) of immune cells with (4S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: (18)F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer–induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x(C)(−) and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal (18)F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. (18)F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. (18)F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal (18)F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68(+)xCT(+) and CD3(+)xCT(+) cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68(+)xCT(+) cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x(C)(−) in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. (18)F-FSPG PET imaging of system x(C)(−) activity may noninvasively assess the IBD activity.

Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, has become a popular target for radionuclide-based theranostic applications in the advanced stages of prostate cancer. We conducted a meta-analysis of the therapeutic effects of PSMA-targeting alpha therapy [225Ac-PSMA radioligand therapy (RLT)] in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: A systematic search was performed using the keywords "mCRPC," "225Ac-PSMA," and "alpha therapy". Therapeutic responses were analyzed as the pooled proportions of patients with more than 50% of prostate-specific antigen (PSA) decline and any PSA decline. Survival outcomes were analyzed by estimating summary survival curves for progression-free survival (PFS) and overall survival (OS). Adverse events were analyzed as the pooled proportions of patients with xerostomia and severe hematotoxicity (anemia, leukocytopenia, and thrombocytopenia). Results: Nine studies with 263 patients were included in our meta-analysis. The pooled proportions of patients with more than 50% of PSA decline and any PSA decline were 60.99% [95% confidence interval (CI) = 54.92-66.83%] and 83.57% (95% CI = 78.62-87.77%), respectively. The estimated mean PFS and mean OS were 9.15 months (95% CI = 6.69-11.03 months) and 11.77 months (95% CI = 9.51-13.49 months), respectively. The pooled proportions of patients with adverse events were 62.81% (95% CI = 39.34-83.46%) for xerostomia, 14.39% (95% CI = 7.76-22.63%) for anemia, 4.12% (95% CI = 0.97-9.31%) for leukocytopenia, and 7.18% (95% CI = 2.70-13.57%) for thrombocytopenia. Conclusion: In our study, around 61% of patients had more than 50% of PSA decline and 84% of patients had any PSA decline after 225Ac-PSMA RLT. The common adverse events in 225Ac-PSMA RLT were xerostomia in 63% of patients and severe hematotoxicity in 4-14% of patients.