Colonic adenocarcinomas: Near-infrared microcatheter imaging of smart probes for early detection - Study in mice

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.