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Updated: Apr 12, 2026
In vivo Imaging of Tumor Angiogenesis using Fluorescence Confocal Videomicroscopy
Published on: September 11, 2013
Evaluation of tumor ischemia in response to an indole-based vascular disrupting agent using BLI and (19)F MRI
Heling Zhou1, Rami R Hallac2, Ramona Lopez1
1Department of Radiology, University of Texas Southwestern Medical Center Dallas, TX 75390, USA.
Abstract:
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.
Insights
A novel vascular disrupting agent, OXi8007, effectively reduces tumor blood flow and oxygen levels in breast cancer models. This agent shows sustained efficacy, outperforming combretastatin A-4P in preclinical studies.
Area of Science:
- Oncology
- Medical Imaging
- Pharmacology
Background:
- Vascular disrupting agents (VDAs) offer a broad-spectrum cancer therapy approach by inducing tumor ischemia and hypoxia.
- A novel VDA, OXi8007, demonstrated rapid tumor vasculature shutdown.
- Further investigation is needed to assess OXi8007's impact on tumor perfusion and oxygenation.
Purpose of the Study:
- To noninvasively assess perfusion and hypoxiation in orthotopic human breast tumor xenografts after OXi8007 administration.
- To compare the efficacy and duration of OXi8007's vascular-disrupting effects with combretastatin A-4P (CA4P).
- To evaluate OXi8007's impact on tumor oxygen levels (pO2) using advanced MRI techniques.
Main Methods:
- Orthotopic human MDA-MB-231/luc breast tumor xenografts were used.
- Dynamic bioluminescence imaging (BLI) assessed tumor perfusion.
- 19F MRI with FREDOM (Fluorocarbon Relaxometry using Echo Planar Imaging for Dynamic Oxygen Mapping) measured tumor pO2 distributions during air and oxygen breathing.
Main Results:
- BLI signal significantly decreased post-OXi8007 administration, indicating reduced perfusion, with effects lasting up to 72 hours.
- Compared to controls, OXi8007 significantly lowered tumor pO2 during oxygen breathing (122 to 34 Torr) and further decreased it during air breathing (17 Torr).
- Intra-tumor heterogeneity in pO2 response was observed, but all regions ultimately became hypoxic, confirming OXi8007's efficacy.
Conclusions:
- OXi8007 demonstrates potent and sustained vascular disrupting effects in preclinical breast cancer models.
- Noninvasive imaging techniques like BLI and FREDOM effectively monitored OXi8007's impact on tumor perfusion and hypoxia.
- The measured pO2 changes suggest OXi8007's potential role in combination therapies for cancer treatment.
