4T1 mouse mammary
adenocarcinomas and Caki-1 human
renal cell carcinomas grown in mouse dorsal window chambers were serially treated with the vascular disrupting agent (VDA)
OXi4503 and their responses compared. The real-time in vivo response was assessed using spectral imaging of microvascular
hemoglobin saturation. To our knowledge this is the first use of spectral imaging technology for investigation of vascular disrupting agents. Previous research showing
tumor size dependence in the treatment response to VDAs suggested that for the size of
tumors used in this study only a moderate response would be observed; however, the
tumors unexpectedly had very different responses to treatment. Caki-1
tumors showed little permanent vessel damage and experienced transient vessel collapse with time-dependent oxygenation changes followed by recovery starting at 6 h
after treatment. Caki-1
tumors did not manifest necrotic avascular regions even after repeated treatments. These results are consistent with those obtained using other imaging modalities and histology. In contrast, similarly sized 4T1
tumors showed extensive vessel disintegration, minor vascular collapse, and a drop in
tumor oxygenation up to 6 h post-treatment, after which reperfusion of collapsed vessels and extensive
vascular remodeling and neovascularization of the
tumor rim occurred from 8-48 h. The completely disintegrated vessels did not recover and left behind avascular and apparently necrotic regions in the
tumor core. Spectral imaging appears to be a useful technique for in vivo investigation of vascular disrupting agents. The differential responses of these two
tumor-types suggest that further investigation of the mechanisms of action of VDAs and individual characterization of
tumor VDA-responses may be needed for optimal clinical use of these agents.