Vascular disrupting agents (VDAs) have been proposed as an effective broad spectrum approach to
cancer therapy, by inducing
ischemia leading to
hypoxia and cell death. A novel VDA (OXi8007) was recently reported to show rapid acute selective shutdown of
tumor vasculature based on color-Doppler ultrasound. We have now expanded investigations to noninvasively assess perfusion and hypoxiation of orthotopic human MDA-MB-231/luc
breast tumor xenografts following the administration of OXi8007 based on dynamic bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). BLI showed significantly lower signal four hours after the administration of OXi8007, which was very similar to the response to
combretastatin A-4P (CA4P), but the effect lasted considerably longer, with the BLI signal remaining depressed at 72 hrs. Meanwhile, control
tumors exhibited minimal change. Oximetry used (19)F MRI of the reporter molecule
hexafluorobenzene and FREDOM (
Fluorocarbon Relaxometry using Echo Planar Imaging for Dynamic
Oxygen Mapping) to assess pO2 distributions during air and
oxygen breathing. pO2 decreased significantly upon the administration of OXi8007 during
oxygen breathing (from 122 ± 64 to 34 ± 20 Torr), with further decrease upon switching the gas to air (pO2 = 17 ± 9 Torr). pO2 maps indicated intra-
tumor heterogeneity in response to OXi8007, though ultimately all
tumor regions became hypoxic. Both BLI and FREDOM showed the efficacy of OXi8007. The pO2 changes measured by FREDOM may be crucial for future study of combined
therapy.