Detection of mice colorectal tumors by endoluminal ultrasound biomicroscopic images and quantification of image augmented gray values following injection of VEGFR-2 targeted contrast agent

Rationale and Objectives: Ultrasound biomicroscopy (UBM) is a noninvasive imaging technique that can be applied in detecting colonic tumors and, once associated with an ultrasound contrast agent (UCA), can identify the molecular expression of cancer-related biomarkers, such as the vascular endothelial growth factor receptor 2 (VEGFR-2). The present work aimed to detect colonic tumors and quantify augmented gray values of endoluminal UBM (eUBM) images from colonic tumors following the injection of VEGFR-2 targeted UCA (VEGFR2-UCA) into a mouse model of colorectal cancer. Material and Methods: A 40 MHz miniprobe catheter inserted through the biopsy channel of a pediatric flexible bronchofiberscope was used to obtain colonoscopic and B-mode eUBM images simultaneously. Seventeen tumor-bearing mice had their colons inspected and six of them were subjected to a VEGFR2-UCA injection to predict VEGFR-2 expression. Results: All animals developed distal colon tumors and eUBM was able to detect all of them and also to characterize the tumors, with 71.4% being in situ lesions and 28.6% being tumors invading the mucosa + muscularis mucosae + submucosa layers, as confirmed by histopathology. After VEGFR2-UCA injection, gray values from the eUBM tumoral images increased significantly (p < 0.01). Tumor sites with increased eUBM image gray values corresponded to areas with increased VEGFR-2 expression, as confirmed by immunohistochemistry. Conclusion: The results confirm eUBM as a powerful noninvasive and real-time tool for detecting colon tumor and its invasiveness and once associated with VEGFR2-UCA may become a tool for the detection of VEGFR-2 expression in colonic tumors