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

Radiology. 2007 Jul;244(1):232-8. doi: 10.1148/radiol.2441052114. Epub 2007 May 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / pathology
  • Animals
  • Cathepsin B*
  • Catheterization / instrumentation
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / pathology
  • Colonoscopy
  • Early Diagnosis
  • Fiber Optic Technology
  • Mice
  • Microscopy, Fluorescence
  • Prospective Studies
  • Spectroscopy, Near-Infrared / methods*
  • Tumor Cells, Cultured

Substances

  • Cathepsin B