RT Journal Article SR Electronic T1 18F-FAC PET selectively images hepatic infiltrating CD4 and CD8 T cells in a mouse model of autoimmune hepatitis JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.118.210328 DO 10.2967/jnumed.118.210328 A1 Jessica R. Salas A1 Bao Ying Chen A1 Alicia Wong A1 Donghui Cheng A1 John S. Van Arnam A1 Owen N. Witte A1 Peter M. Clark YR 2018 UL http://jnm.snmjournals.org/content/early/2018/04/25/jnumed.118.210328.abstract AB Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (18F-FDG and 18F-FAC) and hepatocyte biology (18F-DFA) can visualize and quantify hepatic infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with Concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with 18F-FDG, 18F-FAC, and 18F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis or vehicle were imaged with 18F-FDG, 18F-FAC, and 18F-DFA PET. 18F-FAC PET was performed on mice treated with ConA, and vehicle or dexamethasone. Biopsy samples of patients suffering from autoimmune hepatitis were immunostained for deoxycytidine kinase (dCK). Results: Hepatic accumulation of 18F-FDG and 18F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of 18F-DFA was 41% lower in a mouse model of autoimmune hepatitis compared to control mice. Increased hepatic 18F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic 18F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic 18F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic 18F-FDG accumulation by 109% and decreased hepatic 18F-DFA accumulation by 20% but had no effect on hepatic 18F-FAC accumulation (non-significant 2% decrease). 18F-FAC PET provided a non-invasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients suffering from autoimmune hepatitis express high levels of dCK, a rate-limiting enzyme in the accumulation of 18F-FAC. Conclusion: Our data suggests that PET can be used to non-invasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.