Establishment of an orthotopic syngeneic rat model of hepatocellular carcinoma and its validation with microPET-CT imaging

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) is a global challenge due to rising incidence and high mortality rate among the affected individuals. Establishing successful animal models of HCC is, therefore, crucial for basic and translational studies of HCC. Present study was undertaken to develop orthotopic syngeneic rat HCC model to study new diagnostic and therapeutic strategies for human HCC research. Methods : Rat Novikoff hepatoma cells were injected beneath the capsule of left lobe of liver in fifty-five sprague dawley rats. Study was divided in three phases, 15 Animals in phase-I were injected with 4x10 6 cells in 100µl DMEM, 15 animals in phase-II with 2x10 6 cells in 50µl and 30 animals in phase-III with 3 x10 6 cells in a 100µl DMEM. Tumor induction rate, tumor size and progression and mortality rate was evaluated and assessed using serial µPET-CT imaging till four weeks. F-18 Flurodeoxyglucose was used as metabolic imaging radiotracer and imaging findings were correlated grossly and histologically. Results : Phase-I animals showed 100% tumor induction rate but multiple intrahepatic and intra peritoneal masses with 100% mortality observed. Phase-II animals did not show any tumor. Phase-III animals showed 100% induction rate with controlled and diffused progression of hepatic tumor. CT images and sequential higher flurodeoxyglucose uptake in liver confirmed the progression of tumor. Gross examination and histology confirmed the presence of HCC. Conclusions: N1S1 cell induced orthotopic syngeneic HCC rat model with progressive controlled tumor growth and least mortality rate can be used to study new diagnostic techniques and plan new therapeutic strategies against HCC.