In vivo imaging using a VEGF-based near-infrared fluorescent probe for early cancer diagnosis in the AOM-treated mouse model

Strong vascular endothelial growth factor (VEGF) receptor expression has been found at the sites of angiogenesis, particularly in tumor growth areas. An increase in VEGF receptor-2 is associated with colon cancer progression. The in vivo detection of VEGF receptor is of interest for the purposes of studying carcinogenesis, the efficacy of chemopreventive and therapeutic agents, clinical diagnosis, and therapeutic monitoring. In this study, a novel single chain (sc) VEGF-based molecular probe is utilized in the AOM-treated mouse model of colorectal cancer to study delivery route and specificity for disease. The probe was constructed by site-specific conjugation of a near-infrared dye, Cy5.5, to scVEGF and detected in vivo with a dual-modality optical coherence tomography / laser-induced fluorescence (OCT/LIF) endoscopic system. The LIF excitation source was a 633 nm He:Ne laser and red/near-infrared fluorescence was detected with a spectrometer. OCT was used to obtain two-dimensional longitudinal tomograms at eight rotations in the distal colon. Fluorescence emission levels were correlated with OCT-detected disease in vivo and H&E stained histology slides ex vivo. Specificity for disease was found to be highly dependent on the delivery route. Intravenous injection resulted in poor specificity due to many extra-colon confounders, while colon lavage eliminated most of these. High fluorescence emission intensity was correlated with tumor presence as detected using OCT. Results suggest potential for clinical use to facilitate earlier diagnosis of cancer.