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Abstract
We aimed to explore whether the imaging of antiporter system xC - of immune cells with (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18F-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 xC - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18F-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. 18F-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. 18F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18F-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 xC - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18F-FSPG PET imaging of system xC - activity may noninvasively assess the IBD activity.

Affiliations

Minjung Seo 1, Yeji Kim 2, Byong Duk Ye 3, Sang Hyoung Park 3, Seog-Young Kim 2, Jin Hwa Jung 2, Sung Wook Hwang 3, Sun Young Chae 4, Dong Yun Lee 4, Sang Ju Lee 4, Seung Jun Oh 4, Jihun Kim 5, Ji Young Kim 6, Sae Jung Na 7, Misung Kim 8, Sang-Yeob Kim 2, Norman Koglin 9, Andrew W Stephens 9, Mi-Na Kweon 10, Dae Hyuk Moon 11
1Department of Nuclear Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
2Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
4Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
6Department of Nuclear Medicine, Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Republic of Korea.
7Department of Radiology, Uijeongbu St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
8Department of Pathology, Ulsan University Hospital, Ulsan, Republic of Korea; and.
9Life Molecular Imaging GmbH, Berlin, Germany.
10Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; dhmoon@amc.seoul.kr mnkweon@amc.seoul.kr.
11Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; dhmoon@amc.seoul.kr mnkweon@amc.seoul.kr.