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Radiology. 2007 Jul;244(1):232-8. Epub 2007 May 16.

Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection--study in mice.

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  • 1Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Bldg 149, 13th St, Room 5408, Charlestown, MA 02129, USA.

Abstract

PURPOSE:

To prospectively evaluate the ability of micro-fiberoptic catheters, which simultaneously record white light and near-infrared (NIR) images, to reveal colonic neoplasms after the intravenous administration of activatable "smart" probes that increase in NIR fluorescence subsequent to protease activation.

MATERIALS AND METHODS:

The institutional animal care committee approved all animal experiments. CT26 tumor cells were orthotopically implanted into the descending colon of C57BL6/J mice (n=10). Thirteen days later, mice intravenously received either 2 nmol of a protease-sensing probe that had cathepsin B as a major activator (n=5) or saline (control animals [n=5]). One day later, animals were noninvasively examined to the point of the splenic flexure by using microcatheter imaging. Excised colons were subsequently evaluated with epifluorescence imaging, histologic examination, and cathepsin B immunohistochemistry. Student t test was used for statistical analysis, with P<.05 considered to indicate a significant difference.

RESULTS:

Results with fiberoptic imaging demonstrated that all tumors were visible with the protease-activatable probe, even when they were not readily apparent at white light imaging. A target-to-background ratio (TBR) of 8.86 for tumor to adjacent normal mucosa was achieved in the NIR channel after probe administration (P=.001), whereas white light images resulted in a TBR of 1.14 (P>.5) based on luminosity. The tumoral NIR fluorescence intensity was more than 30-fold greater in probe-injected animals than in control animals, indicating that essentially all of the signal recorded in lesions was from activatable probe administration. Results of immunohistochemistry confirmed cathepsin B overexpression in the tumor compared with adjacent mucosa.

CONCLUSION:

The use of NIR imaging microcatheters combined with protease-activatable smart probes results in a beacon effect that highlights tumors with high TBRs; this technique thus may be a potentially useful adjunct to white light colonoscopy in the future.

(c) RSNA, 2007.

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PMID:
17507718
[PubMed - indexed for MEDLINE]

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