Regulation of Hepatobiliary Transport Activity and Noninvasive Identification of Cytokine- Dependent Liver Inflammation

Many diseases are associated with cytokine release after in-flammatory infiltration, which perturbs organ function. Radioli-gands capable of noninvasive tracking to assess the integrity of specific biochemical pathways offer potent ways to establish such perturbing mechanisms. Methods: To demonstrate regu-lation of hepatobiliary transport in disease, we used 99mTc-mebrofenin in a carbon tetrachloride–induced liver injury model in Fischer 344 rats. Healthy rats served as control animals. Image analysis was used to determine 99mTc-mebrofenin han-dling. Liver tests and histologic analysis were used for grading liver injury and hepatic fibrosis. To address the role of inflam-matory cytokines, we used in vitro assays with 99mTc-mebrofe-nin-loaded primary rat hepatocytes. Results: In healthy rats, 99mTc-mebrofenin was promptly excreted, and after 1 h only 20 % 5 % (mean SD) of peak 99mTc-mebrofenin activit