In vivo spectral and fluorescence imaging microscopy of tumor microvessel blood supply and oxygenation changes following vascular targeting agent treatment

The formation of new microvasculature is essential for a tumor mass to grow. Vascular targeting agents (VTAs), including anti-angiogenic drugs and vascular disrupting agents, aim to either inhibit new vasculature growth or destroy existing vasculature, respectively. Because the mechanisms for anti-angiogenic drugs and vascular disrupting agents are complementary, analysis of these drugs used together is under investigation for the enhanced treatment of tumors in comparison to each treatment alone. The preclinical evaluation of the effects of VTAs on tumor growth in small animal models is vital for the development of effective drugs for clinical use. In vivo hyperspectral imaging microscopy of hemoglobin saturation has been used previously to investigate the efficacy of VTAs through analysis of tumor microvessel oxygenation after drug administration. Combining this imaging modality with first-pass fluorescence angiographic imaging can give additional important information about the vessel morphology and blood flow changes that occur after VTA treatment, thus elucidating the relationship between microvessel structure changes and oxygenation. In this study, we report the combined use of hyperspectral and first pass fluorescence angiographic imaging to examine the relationship between vessel morphology and oxygenation of human prostate cancer tumors in mice following treatment with vascular disrupting agents, OXi4503, and anti-VEGF angiogenesis inhibitor, cediranib. Imaging of the tumors is completed before treatment as well as in the days following treatment.