In vivo spectral and fluorescence microscopy comparison of microvascular function after treatment with OXi4503, Sunitinib and their combination in Caki-2 tumors.

Jennifer A Lee,Nikolett M Biel,Dietmar W Siemann,Raymond T Kozikowski,Brian S Sorg

doi:10.1364/boe.5.001965

Abstract

Vascular targeting agents on their own have been shown to be insufficient for complete treatment of solid tumors, emphasizing the importance of studying the vascular effects of these drugs for their use with conventional therapies in the clinic. First-pass fluorescence imaging combined with hyperspectral imaging of hemoglobin saturation of microvessels in the murine dorsal window chamber model provides an easily implementable, low cost method to analyze tumor vascular response to these agents in real-time. In this study, the authors utilized these methods to spectroscopically demonstrate distinct vessel structure, blood flow and oxygenation changes in human Caki-2 renal cell carcinoma following treatment with OXi4503 alone, Sunitinib alone and both drugs together. We showed that treatment with OXi4503 plus Sunitinib destroyed existing tumor microvessels, inhibited blood vessel recovery and impaired Caki-2 tumor growth significantly more than either treatment alone.

Highlights

Various pathologies are characterized by the formation of abnormal vascular development
Tumor growth dependence on vascular formation and acquisition of adequate blood supply has led to significant effort towards the development of vascular targeting agents (VTAs) to treat solid tumors [1,2]
Two major classes of VTAs are vascular disrupting agents (VDAs) which act to destroy existing tumor vasculature by targeting their rapidly proliferating endothelial cells and angiogenic inhibiting agents (AIAs) that aim to inhibit the development of new tumor vasculature by targeting angiogenic stimulators and cytokines [3,4,5,6,7,8,9]

Summary

Introduction

Various pathologies are characterized by the formation of abnormal vascular development. Tumor growth dependence on vascular formation and acquisition of adequate blood supply has led to significant effort towards the development of vascular targeting agents (VTAs) to treat solid tumors [1,2]. Two major classes of VTAs are vascular disrupting agents (VDAs) which act to destroy existing tumor vasculature by targeting their rapidly proliferating endothelial cells and angiogenic inhibiting agents (AIAs) that aim to inhibit the development of new tumor vasculature by targeting angiogenic stimulators and cytokines [3,4,5,6,7,8,9]. Preclinical investigation into the use of these agents in combination showed enhanced tumor growth delay in comparison to either treatment alone, yet tumors still eventually grew to endpoint volumes [13,14]

Methods

Results

Conclusion