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.
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.
Marlene
M
Wiart
Laure S
LS
Fournier
Viktor Y
VY
Novikov
David M
DM
Shames
Timothy P
TP
Roberts
Yanjun
Y
Fu
David R
DR
Shalinsky
Robert C
RC
Brasch
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