TCRT August 2004

category image Volume 3
No. 4 (p 309-410)
August 2004
ISSN 1533-0338
Magnetic Resonance Imaging

Magnetic Resonance Imaging Detects Early Changes in Microvascular Permeability in Xenograft Tumors after Treatment with the Matrix Metalloprotease Inhibitor Prinomastat (p 377-382)

Macromolecular contrast medium-enhanced magnetic resonance imaging was applied to monitor the effect of matrix metalloprotease (MMP) inhibition on microvascular characteristics of human breast cancers implanted in athymic rats. Twice-daily intraperitoneal administration of Prinomastat over 1.5 days induced significant declines in MRI-assayed microvascular permeabilities (p<0.05); but this leak suppression effect had extinguished by the 10th day of MMP treatment using the same dose and time schedule. Results demonstrate that Prinomastat produces a rapid but transient decrease in tumor vascular permeability. Contrast-enhanced MRI using macromolecular contrast medium may prove useful as a biomarker for the dynamic MMP biological effect in cancers.

Key words: Magnetic resonance imaging, Contrast medium, Matrix metalloprotease MMP, Prinomastat AG3340.

Marlene Wiart, Ph.D.1
Laure S Fournier, M.D.1
Viktor Y Novikov, M.D.1
David M Shames, M.D.1
Timothy P Roberts, Ph.D.1
Yanjun Fu, Ph.D.1
David R Shalinsky, Ph.D.2
Robert C Brasch, M.D.1*

1Center for Pharmaceutical and Molecular Imaging
Department of Radiology, Box 0628
University of California, San Francisco
513 Parnassus Avenue
San Francisco, CA 94143-0628 USA
2Department of Research Pharmacology
Pfizer Global Research and Development
La Jolla/Agouron Pharmaceuticals, Inc.
4245 Sorrento Valley
La Jolla, CA 92121 USA
*robert.brasch@radiology.ucsf.edu

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