Two Vascular Disrupting Agents at a Clinically Equivalent Dose on Rodent Liver Tumors: Comparison of Therapeutic Outcomes with Multiple MRI Biomarkers

Huaijun Wang¹, Junjie Li¹, Feng Chen¹, Frederik De Keyzer¹, Jie Yu¹, Yuanbo Feng¹, Yansheng Jiang¹, Guy Marchal¹, Yicheng Ni¹

This study aimed to compare tumoricidal events after 2 lead vascular- targeting-agents (VDAs), Combretastatin-A-4-phosphate (CA4P) and ZD6126 at a clinically-equivalent-dose (CED) in tumors with multiple MRI biomarkers correlated with postmortem microangiography and histopathology. Rhabdomyosarcomas in rat liver were treated with either VDA. Therapeutic outcomes were evaluated morphologically and functionally with 1.5T-MRI. Diffusion-weighted-imaging and dynamic-contrast-enhanced-MRI successfully monitored vascular-shutdown at 1h after VDA treatment, prior to the advent of morphological change of tumor size at 120h, which was verified with postmortem techniques. CED of CA4P has longer vascular-shutdown effect until 48h than ZD6126, leading to significantly different tumor growth delay at 120h.