Therapeutic Vascular Targeting and Irradiation: Correlation of MRI and Tissue Changes at Cellular and Molecular Levels to Optimizing Outcomes
Abstract
Vascular targeting agents (VTA) are new types of anticancer drugs that act on existing tumor vasculature, causing vascular disruption, which ultimately leads to extensive ischemic tumor cell death. One major goal of this project is to precisely assess the dynamic changes in vascular perfusion and oxygenation at different time points following VTA in breast tumors. In vivo non-invasive MRI approaches observed significant decrease in signal intensity by DCE (dynamic contrast enhanced) MRI and ADC (apparent diffusion coefficient) values by diffusion weighted MRI at 2hr after an injection of combretastatin A4 phosphate (CA4P) at 30 mg/kg. Most importantly, 19FNMR oximetry showed that tumor oxygenation started to drop significantly at 90 min and became worst at 2hr after the injection, compared to pretreated baseline level. The pO2 improved significantly 24hr later. These MRI data are comparable to histological and immunohistochemical results showing a significant decrease in perfused vessels detected by Hoechst dye 33342 at 2hr after CA4P. We believe in vivo MRI monitoring of tumor vasculature and oxygenation in response to VTA will be very important to optimize timing for combined VTAs with irradiation. While dynamic contrast MRI indicates vascular shut down, the critical pO2 measurements are potentially more important.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427291
Entities
People
- Dawen Zhao
Organizations
- University of Texas at Dallas