Near-Infrared Confocal Laser Endomicroscopy Detects Colorectal Cancer via an Integrin alpha sub(v) beta sub(3) Optical Probe

Purpose: 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 alpha sub(v) beta sub(3) optical probe in near-infrared fluorescence (NIRF) confocal laser endomicroscopy (CLE) for tumour detection in a rodent model. Procedures: 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 660 nm and an antagonistic small-molecule integrin alpha sub(v) beta sub(3) NIRF contrast agent. Results: 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 alpha sub(v) beta sub(3) 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. Conclusions: Targeting integrin alpha sub(v) beta sub(3) 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.