[18F]FDG PET imaging evaluation on non-alcoholic fatty liver disease and hepatocellular carcinoma model treated with sorafenib

Abstract

Aim: Evaluate the effect of sorafenib in a rat model of non-alcoholic fatty liver disease (NAFLD) related to hepatocellular carcinoma (HCC) by quantifying the correlation between changes in glucose metabolism on PET imaging and degree of tumor differentiation. Methods: NAFLD related HCC was induced by the combination of high fat and choline deficient diet with diethylnitrosamine (100 mg/L) for 16 weeks. Then carcinogenic stimuli were suspended, liver nodules were identified by abdominal ultrasound and two groups were randomized: control (n = 10) and sorafenib (n = 20). Rats received daily gavage administration of 1 mL saline or sorafenib (5 mg/kg/day) for more 3 weeks. After treatment, [ 18 F]FDG PET scan was performed on animals. Results: [ 18 F]FDG uptake was lower in the sorafenib group than that in the control group (3.3 ± 0.48 vs. 5.5 ± 1.5, P = 0.01). Direct correlation was found between poorly-differentiated HCC and TumorSUVmax/MuscleSUVmax ratio (R 2 = 0.54, P = 0.006). Treatment was associated with significantly more residual tumors that were well differentiated (Grades I/II) than in the untreated control group (39% vs. 5%, respectively, P = 0.01). Conclusion: Sorafenib shows promise as a treatment for reducing the aggressiveness of HCC as demonstrated by [ 18 F] FDG PET and immunohistochemistry.

Preclinical Models of Liver Câncer

“…Likewise, the combination of DDC and N-nitrosodiethylamine (NDE) induces HCC faster than DDC alone and maintains the specific features of diet-induced liver injury, which are steatosis and inflammation (29)(30)(31) . Our group published a model that combined diet and DEN that replicates the sequence of NASH, fibrosis, cirrhosis and HCC, with anti-CK 19 expression that suggests proliferation of oval cells after 16 weeks (29) and, more recently tested the effectiveness of sorafenib using PET-Scan in this model (32) .…”