Detecting Vascular-Targeting Effects of the Hypoxic Cytotoxin Tirapazamine in Tumor Xenografts Using Magnetic Resonance Imaging
- Department of Physics and Astronomy, University of British Columbia, Vancouver (Canada)
- Medical Biophysics Department, British Columbia Cancer Research Centre, Vancouver (Canada)
Purpose: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). Methods and Materials: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K{sup trans}) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. Results: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K{sup trans} and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K{sup trans} and IAUC values. Conclusions: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.
- OSTI ID:
- 21276885
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 74, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2008.11.068; PII: S0360-3016(08)03812-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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