Evaluation of tumor ischemia in response to an indole-based vascular disrupting agent using BLI and 19F MRI

American Journal of Nuclear Medicine and Molecular Imaging

Rebecca Denney¹  Li Liu¹  Mary Lynn Trawick¹  Kevin G Pinney¹  Heling Zhou¹  Edward E Graves¹  Matthew T MacDonough¹  Ralph P Mason¹  Rami R Hallac¹  Ramona Lopez¹  Li Li¹ 

关键词: Vascular disrupting agents (VDAs);    bioluminescence imaging (BLI);    oximetry;    hypoxia;    19F MRI;    hexafluorobenzene;    OXi8007;    CA4P;   

DOI  :  

学科分类：过敏症与临床免疫学

来源: e-Century Publishing Corporation

【 摘 要 】

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 ¹⁹F 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.

【 授权许可】

Unknown