Combination of an Integrin-Targeting NIR Tracer and an Ultrasensitive Spectroscopic Device for Intraoperative Detection of Head and Neck Tumor Margins and Metastatic Lymph Nodes.

• Type of Material: Article
• Authors: Younghyoun Yoon, Emory University; Aaron M. Mohs, Georgia Institute of Technology; Michael C. Mancini, Georgia Institute of Technology; Shuming Nie, Emory University; Hyunsuk Shim, Emory University
• Language: English
• Date: 2016-09
• Publisher: Grapho Publications, LLC.
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors. Published by Grapho Publications, LLC
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.18383/j.tom.2016.00253
• Title of Journal or Parent Work: Tomography : a journal for imaging research
• ISSN: 2379-1381
• Volume: 2
• Issue: 3
• Start Page: 215
• End Page: 222
• Grant/Funding Information: This work was supported by grants from the National Cancer Institute (R01CA165306 to H.S., R01CA163256 to S.N., and K99CA153916 to A.M.).
• Keywords: metastatic; infiltrative; near-infrared; intraoperative guidance; lymph nodes; tumor margins; RGD; head and neck cancer

Abstract

Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%-30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer-device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50-100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes.