Abstract 2257: Optical imaging guidance of tumor resection margin for head and neck cancer
Authors: Younghyoun Yoon, Aaron Mohs, Zhongxing Liang, Michael C. Mancini, Doohyung Lee, Georgia Z. Chen, Daniel J. Brat, Amy Y. Chen, Shuming Nie, Hyunsuk Shim
Journal: Cancer Research (2010)

Abstract Traditional methods for assessing adequacy of head and neck tumor resection rely upon intraoperative palpation or visualization. Positive margins are strongly associated with recurrence and poor patient survival. To ensure the complete tumor removal, surgeons may resect additional peritumoral tissues. During the past decade, intraoperative pathologic consultation by frozen section has become standard. Each round of consultation takes 20 minutes and the average number of such consultation is 3 − 4 per operation, which prolongs the procedure. Two additional potential problems are: (1) it is impossible to locate all cohorts of infiltrating tumor cells; (2) the final pathology may reveal a positive margin when the frozen section was negative. Currently 20 − 30% of head and neck patients that undergo surgery still leave the operating room with an incomplete resection. Thus, major opportunities exist to develop a deep tissue imaging near infrared (NIR) agent and an intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The advantage of using optical imaging over radioisotopes is that it avoids continuous exposure of operating room personnel to radioactivity. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. We exploited integrin overexpression on infiltrating cancer cells for intraoperative detection of tumor margins. We tested a new optical instrumentation in conjunction with the integrin-targeted NIR dye, RGD-IRDye800CW, for assessing malignant tumor margins in an orthotopic head and neck cancer animal model. RGD peptides have high binding specificity to integrin αvβ3. For intraoperative tumor margin detection, we developed an intraoperative wavelength-resolved NIR imaging system. This device offers real-time, portable detection of tumor margins with high stability, faster throughput, and better co-registration than other imaging methods. In our animal model, the tumors infiltrated to the mylohoid neck muscle beyond tumor boundaries and the primary tumor resection left residual infiltrating tumors and metastatic lymph nodes behind, which were easily detected by our technology. We also found NIR signal in several spots of the lungs from the same mice. Histological analysis in correlation to imaging results support that we can detect extremely small cohorts of 20 − 50 tumor cells in intraoperative settings with high specificity. Thus our technology will be ideal in detecting tumor margins intraoperatively because the average number of tumor cells in invading cohorts is 50 − 100 and NIR penetration depth is about 3 − 5 cm. Of note, we found that NIR signals from the RGD peptides were stronger at the edge (rim) of tumors than the center; therefore, the integrin-targeted imaging probe will allow us to detect the tumor margins as well as infiltrating cohorts of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2257.