Magnetic resonance imaging detects early changes in microvascular permeability in xenograft tumors after treatment with the matrix metalloprotease inhibitor Prinomastat.
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 10(th) 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.
Wiart
Marlene
M
Center for Pharmaceutical and Molecular Imaging, Department of Radiology, Box 0628, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0628, USA.
Fournier
Laure S
LS
Novikov
Viktor Y
VY
Shames
David M
DM
Roberts
Timothy P
TP
Fu
Yanjun
Y
Shalinsky
David R
DR
Brasch
Robert C
RC
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002199:Capillary Permeability; D002455:Cell Division; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods*; D061965:Matrix Metalloproteinase Inhibitors; D008833:Microcirculation; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy; D009930:Organic Chemicals / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude; D013223:Statistics as Topic; D013997:Time Factors
D000970:Antineoplastic Agents; D003287:Contrast Media; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; C113282:prinomastat