Targeted Imaging of Colonic Tumors in Smad3−/− Mice Discriminates Cancer and Inflammation
The peripheral benzodiazepine receptor (PBR) is a trans-mitochondrial membrane protein that modulates steroid biosynthesis. Recently, up-regulation and nuclear localization of PBR has been shown to be associated with colon, prostate, and breast cancer. PBR has been targeted by the exogenous syntheti...
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Published in | Molecular cancer research Vol. 5; no. 4; pp. 341 - 349 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.04.2007
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Subjects | |
Online Access | Get full text |
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Summary: | The peripheral benzodiazepine receptor (PBR) is a trans-mitochondrial membrane protein that modulates steroid biosynthesis.
Recently, up-regulation and nuclear localization of PBR has been shown to be associated with colon, prostate, and breast cancer.
PBR has been targeted by the exogenous synthetic ligand, PK11195, for various purposes including imaging. To capitalize on
these observations, we developed a high-throughput, noninvasive, in vivo imaging approach to detect spontaneously arising colonic tumors in mice using a novel PBR-targeted molecular imaging agent
(NIR-conPK11195). NIR-conPK11195 localized and was retained in colonic adenomas and carcinomas in Smad3 −/− mice but not in non-neoplastic hamartomas or chronically inflamed colonic tissue. Using a fluorescence signal-to-noise ratio
of ≥4-fold 13 h after injection of the agent, we detected colonic tumors with a sensitivity of 67% and a specificity of 86%
in a cohort of 37 Smad3 −/− mice and control littermates. Furthermore, using oral administration of dextran sulfate to induce colonic inflammation, we
showed that the clearance profile of NIR-conPK11195 distinguished transient uptake in inflammatory tissue from longer term
retention in tumors. Taken together, these results indicate that NIR-conPK11195 is a promising optical molecular imaging tool
to rapidly screen for colonic tumors in mice and to discriminate inflammation from cancer. (Mol Cancer Res 2007;5(4):341–9) |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1541-7786 1557-3125 |
DOI: | 10.1158/1541-7786.MCR-06-0225 |