Linked Life Data

10987312

Source:http://linkedlifedata.com/resource/pubmed/id/10987312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2000-9-28
pubmed:abstractText
The single biggest challenge facing in vivo imaging techniques is to develop biocompatible molecular beacons that are capable of specifically and accurately measuring in vivo targets at the protein, RNA, or DNA level. Our efforts have focused on developing activatable imaging probes to measure specific enzyme activities in vivo. Using cathepsin D as a model target protease, we synthesized a long-circulating, synthetic graft copolymer bearing near-infrared (NIR) fluorochromes positioned on cleavable substrate sequences. In its native state, the reporter probe was essentially nonfluorescent at 700 nm due to energy resonance transfer among the bound fluorochromes (quenching) but became brightly fluorescent when the latter were released by cathepsin D. NIR fluorescence signal activation was linear over at least 4 orders of magnitude and specific when compared with scrambled nonsense substrates. Using matched rodent tumor models implanted into nude mice expressing or lacking the targeted protease, it could be shown that the former generated sufficient NIR signal to be directly detectable and that the signal was significantly different compared with negative control tumors. The developed probes should find widespread applications for real-time in vivo imaging of a variety of clinically relevant proteases, for example, to detect endogenous protease activity in disease, to monitor the efficacy of protease inhibitors, or to image transgene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4953-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10987312-Animals, pubmed-meshheading:10987312-Cathepsin D, pubmed-meshheading:10987312-Fluorescent Dyes, pubmed-meshheading:10987312-Image Processing, Computer-Assisted, pubmed-meshheading:10987312-Mice, pubmed-meshheading:10987312-Mice, Nude, pubmed-meshheading:10987312-Neoplasm Transplantation, pubmed-meshheading:10987312-Neoplasms, Experimental, pubmed-meshheading:10987312-Oligopeptides, pubmed-meshheading:10987312-Peptide Hydrolases, pubmed-meshheading:10987312-Polyethylenes, pubmed-meshheading:10987312-Polylysine, pubmed-meshheading:10987312-Rats, pubmed-meshheading:10987312-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10987312-Spectroscopy, Near-Infrared, pubmed-meshheading:10987312-Substrate Specificity, pubmed-meshheading:10987312-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
In vivo imaging of proteolytic enzyme activity using a novel molecular reporter.
pubmed:affiliation
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't