Neuroinflammation in acute hepatic encephalopathy rats: imaging and therapeutic effectiveness evaluation using 11 C-PK11195 and 18 F-DPA-714 micro-positron emission tomography.

Neuroinflammation has an important influence in pathogenesis of acute hepatic encephalopathy (AHE). 11 C-PK11195 and 18 F-DPA-714 targeted to translocator protein (TSPO) have potential application in positron emission tomography (PET) as a molecular probe of neuroinflammation. The aim of this study was to compare these two radiotracers and their effectiveness in detecting neuroinflammation for the imaging of AHE rat models. Furthermore, using the new radiotracer 18 F-DPA-714, we analyzed the effectiveness of therapeutic treatment for neuroinflammation in AHE. First, we performed a comparative study of 11 C-PK1195 and 18 F-DPA-714 PET to image neuroinflammation in AHE rats induced by thioacetamide. Twenty-four rats were divided into either control group (n = 12) or AHE group (n = 12). Next, each group was subdivided depending on the radiotracer used during PET imaging (n = 6). Radiotracer uptake values encompassing the whole brain were compared. Lastly, we used the optimized tracer to monitor anti-neuroinflammation effects in AHE-induced rats. Forty-six rats were divided into four groups: [normal saline (NS) group (n = 13), minocycline (MINO) group (n = 11), dexamethasone (DEXA) group (n = 11), MINO+DEXA group (n = 11)]. 18 F-DPA-714 PET was performed and the uptake values were calculated. The rotarod test, biochemical indices, and histopathological examinations were quantitatively measured and compared. AHE rats showed reduced motor ability, elevated ammonia levels, and higher liver function indices (all P < 0.05) with unchanged inflammatory factors (all P > 0.05), compared to control group. Both 11 C-PK11195 and 18 F-DPA-714 PET can detect neuroinflammation of AHE rats. Behavioral studies showed that MINO and/or DEXA improved the motor ability in AHE rats (P < 0.05); however, no differences were found for liver function or inflammatory markers among the four groups (all P > 0.05). The average uptake values of whole brain and multiple brain areas in the MINO+DEXA group were lower compared to all other groups (all P < 0.05), which was demonstrated by CD11b stains of microglia. Our results show that both 11 C-PK11195 and 18 F-DPA-714 PET can detect neuroinflammation in AHE-induced rat models. Additionally, the combined use of minocycline and dexamethasone can effectively inhibit neuroinflammation in AHE-induced rats, which can be sensitively monitored by 18 F-DPA-714 PET.