Authors
Bénédicte F Jordan, Matthew Runquist, Natarajan Raghunand, Amanda Baker, Ryan Williams, Lynn Kirkpatrick, Garth Powis, Robert J Gillies
Publication date
2005/5/1
Journal
Neoplasia
Volume
7
Issue
5
Pages
475-485
Publisher
Elsevier
Description
PX-478 is a new agent known to inhibit the hypoxiaresponsive transcription factor, HIF-1α, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing human xenografts were treated either with PX-478 or vehicle, and imaged over time. DW imaging was performed at three b values to generate apparent diffusion coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent, BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability within 2 hours after treatment, which …
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