Near-Infrared Confocal Laser Endomicroscopy Detects Colorectal Cancer via an Integrin αvβ 3 Optical Probe.

Abstract

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths in industrialized countries. The identification of small polyps and neoplasms with non-polypoid morphology remains to be a serious challenge, as about a quarter of them are missed during routine colonoscopy. The aim of this study was to evaluate the application of an integrin αvβ3 optical probe in near-infrared fluorescence (NIRF) confocal laser endomicroscopy (CLE) for tumour detection in a rodent model. In a novel orthotopic CRC mouse model, tumour growth was monitored by bioluminescence imaging and by colonoscopy employing a rigid white-light endoscope, tumour development was scored by total number and size of tumours. Furthermore, NIRF CLE was established using a fibre probe attached to a confocal laser scanner operating at 660nm and an antagonistic small-molecule integrin αvβ3 NIRF contrast agent. Three CRC cell lines of different histological origin were successfully implanted in nude mice, proving the power of this new orthotopic model. Whole body NIRF images of tumour-bearing mice showed specific high accumulation of the integrin αvβ3 probe in regions of tumour growth, colocalizing with the bioluminescent signal. Molecular imaging by means of a CLE fibre probe allowed distinguishing normal mucosa structures from tumour tissue, as confirmed by quantitation of fluorescence intensities and histology. Targeting integrin αvβ3 in a molecular imaging approach was shown to be effective for CRC detection. Use of molecular guidance in near-infrared CLE represents a promising route to improving detection rates.