[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, [¹⁸F]FDG PET scan was performed on animals.

Results: [¹⁸F]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 (R² = 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 [¹⁸F]FDG PET and immunohistochemistry.

Keywords

Animal model / hepatocellular carcinoma / liver steatosis / non-alcoholic fatty liver disease / positron emission tomography / sorafenib

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