Abstract No. 135 - Optimization of a translational rat model of hepatocellular carcinoma and transarterial embolization

Abstract

Improving endovascular therapeutic options for hepatocellular carcinoma (HCC) requires reproducible animal models that recapitulate human disease and allow transarterial embolization (TAE) that mimics techniques used in patients. Diethylnitrosamine (DEN)-induced rat models of HCC recapitulate human disease; however, the severity of the induced HCC limits its use for survival studies. The purpose of this study was to refine a rat model of DEN-induced HCC with respect to DEN dose and TAE with respect to technique. 112 male Wistar rats were administered ad libitum 0.01% DEN in water for 12 weeks. Following the diet, 45 rats received weekly T2-MRI to monitor the development of HCC. Upon development of a ≥0.5cm tumor, rats underwent arteriography and selective TAE with microspheres via carotid or femoral artery catheterization. Rats were retrospectively divided into 4 groups (<350g, 350-400g, 400-450g, >450g) based on starting weight. The health, tumor latency and survival of these groups were compared while the procedure time and periprocedural mortality of the two embolization techniques were compared. No significant differences were found with respect to animal health based on weight gain and grooming or tumor latency among the four groups (p = 0.242). A significant difference was found in survival with rats in the 400-450g and >450g groups living longer than rats in the smallest weight group (avg. 109d vs 89d; p = 0.0097 and 124d vs 89d; p<0.0001, respectively). No significant difference was found in periprocedural mortality for rats undergoing femoral or carotid access; however, procedure times were significantly shorter for rats undergoing TAE via a femoral approach (avg. 75 ± 33min vs. 127 ± 24min; p = 0.0015). A reduced relative dose of DEN resulted in improved survival without compromising the health of the animal or tumor latency while the application of a femoral approach for TAE resulted in decreased procedure time while more nearly mimicking TAE used in the clinic. Together, these modifications provide a translational small animal model of HCC and TAE that can be applied for survival studies.