In vivo molecular target assessment of matrix metalloproteinase inhibition.

TitleIn vivo molecular target assessment of matrix metalloproteinase inhibition.
Publication TypeJournal Article
Year of Publication2001
AuthorsBremer C, Tung CH, Weissleder R
JournalNat Med
Volume7
Issue6
Pagination743-8
Date Published2001 Jun
ISSN1078-8956
KeywordsAnimals, Antineoplastic Agents, Cell Line, Diagnostic Imaging, Fibrosarcoma, Fluorescence, Fluorescent Dyes, Humans, Mammary Neoplasms, Experimental, Matrix Metalloproteinase 2, Matrix Metalloproteinase Inhibitors, Matrix Metalloproteinases, Mice, Mice, Nude, Neoplasms, Experimental, Organic Chemicals, Peptides, Protease Inhibitors, Spectroscopy, Near-Infrared
Abstract

A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AG3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors.

DOI10.1038/89126
Alternate JournalNat Med
PubMed ID11385514
Grant ListCA088365 / CA / NCI NIH HHS / United States
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065