1: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):529-36. 

The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12)
decreases vascular permeability in tumor xenografts monitored by dynamic
contrast enhanced magnetic resonance imaging.

Jordan BF, Runquist M, Raghunand N, Gillies RJ, Tate WR, Powis G, Baker AF.

Department of Biochemistry, University of Arizona Health Sciences Center,
Tucson, AZ 85724, USA.

PURPOSE: The purpose of this study was to use dynamic contrast enhanced magnetic
resonance imaging (DCE-MRI) to measure changes in tumor xenograft permeability
produced by the antitumor thioredoxin-1 (Trx-1) inhibitor 1-methylpropyl
2-imidazolyl disulfide (PX-12) and to assess the relationship to Trx-1 and
vascular endothelial growth factor (VEGF) levels. EXPERIMENTAL DESIGN: DCE-MRI
was used to monitor the dynamics of gadolinium-diethylenetriaminepentaacetic
acid coupled bovine serum albumin as a macromolecular contrast reagent to
measure hemodynamic changes in HT-29 human colon xenografts in immunodeficient
mice treated with PX-12. Blood vessel permeability was estimated from the slope
of the enhancement curves, and tumor vascular volume fraction from the ordinate.
Tumor Trx-1 and VEGF was also measured. RESULTS: PX-12 caused a rapid 63%
decrease in the average tumor blood vessel permeability within 2 hours of
administration. The decrease lasted 24 hours and had returned to pretreatment
values by 48 hours. The changes in vascular permeability were not accompanied by
alterations in average tumor vascular volume fraction. There was a decrease in
tumor and tumor-derived VEGF in plasma at 24 hours after treatment with PX-12,
but not at earlier time points. However, tumor redox active Trx-1 showed a rapid
decline within 2 hours following PX-12 administration that was maintained for 24
hours. CONCLUSION: The rapid decrease in tumor vascular permeability caused by
PX-12 administration coincided with a decrease in tumor redox active Trx-1 and
preceded a decrease in VEGF. DCE-MRI responses to PX-12 in patients of Trx-1
inhibition at early time points and decreased VEGF at later times, may be useful
to follow tumor response and even therapeutic benefit.

PMID: 15701837 [PubMed - in process]