Detection and Pathologic Evaluation of Sentinel Lymph Nodes in the VX2 Tumor Model Using a Novel Ultrasound/Near-Infrared Dual-Modality Contrast Agent

Abstract

This study was conducted with the aim of developing a microbubble agent for near-infrared (NIR) fluorescence and ultrasound dual-modality contrast microbubbles applicable to imaging of sentinel lymph nodes in the VX2 rabbit tumor model. Specific ligands of phosphatidylserine (PS) and Cy7 NIR fluorescent dyes with long emission wavelengths (750–900 nm) were conjugated to the surface of ultrasound contrast microbubbles (MBs), termed Cy7 PS MBs. Ultrasound lymphography and NIR fluorescence imaging were performed using subcutaneous injection of Cy7 PS MBs to visualize the sentinel lymph node. Sentinel lymph node detection rates using the patent blue method, ultrasound lymphography and NIR fluorescence imaging were 95%, 79% and 95%, respectively, and sensitivity was 87%, 74% and 92%, respectively. With 2-D ultrasound, the diagnostic sensitivity for detection of sentinel lymph node metastases was 60% and the specificity was 74%, whereas Cy7 PS MB-enhanced ultrasound had a sensitivity of 80% and a specificity of 87%. The results indicate that dual-modality Cy7 PS MBs combined with ultrasound lymphography and NIR fluorescence may be useful in the detection of normal and metastasized sentinel lymph nodes.