Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

Abstract

We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55+/-0.88 days and final size of 216.2+/-150.4 mm(3) at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system.