Abstract LB-208: Open air fluorescence imaging of tumors using a new, hands-free translational imaging system
Authors: Meganck Jeffrey A. , Vasquez Kristine , Peterson Jeffrey , Condron Chris , Behrooz Ali , Kempner Josh , de Lille Alexandra , Tan Yiyong , Harvey Pete , Gu Hongyan , Kennedy Paul , Roxo Mathew , Faqir Ilias , Zhang Yan , Mirkin Leo , Miller Peter , Yared Wael 
Published: August 2015

Abstract
Intraoperative tumor resection currently relies on the ability of a surgeon to visually detect and/or palpate the tumor and tumor margins. Small tumor nodules can be missed or tumor margins may be inadequately removed, resulting in the need for secondary treatment. Intraoperative fluorescence imaging can help improve the initial resection and, therefore, both improve outcomes and reduce cost. Unconjugated fluorescent dyes have been previously used for this type of study to identify tumors in first-in-human studies. However, dyes conjugated to a targeting moiety have better specificity for the tumor itself and provide better guidance for the surgeon to locate the tumor and remove margins.
The new Solaris imaging system is an open air fluorescence imaging instrument designed specifically for intraoperative imaging in small to large animals. The system supports 4 different fluorescence channels to image common dyes (e.g. indocyanine green [ICG] and Fluorescein isothiocyanate [FITC]) and more unique near-infrared (NIR) fluorescent dyes. All of these can be imaged in ambient light to achieve sensitivities of 10 nM for single, long exposures and 10-100 nM for videos. The imaging head is attached to an adjustable arm so that it be can be positioned 75 cm above the object plane, far enough to be considered outside of the sterile field. The imaging head also has two cameras for simultaneous fluorescence and bright field (color) imaging; these images can be overlaid in the software. Single, long exposure images acquired from 2 different wavelengths can be overlaid to enable multiplexing and improve tumor identification; previously published studies have shown this to be useful for sentinel lymph node detection. For FITC, a custom liquid crystal tunable filter (LCTF) is included in the system in tandem with spectral unmixing software to separate tissue autofluorescence from fluorescence emitted by the dye.
Although this system is designed for larger animals, proof of concept intraoperative tumor resection has been performed in rodents. Subcutaneous tumors have been resected while imaging mice injected with either the targeted agent IntegriSense™ 680 or the activatable agent ProSense® 750. To investigate a more challenging model, tumor cell lines have also been implanted intrasplenically in rats. After injection with either the targeted agent BombesinRSense™ 680 or the activatable agent MMPSense® 750, deep tissue tumors can be identified intraoperatively and removed. Both the residual tumor bed (in vivo) and the resected tumors (ex vivo) can be imaged to confirm complete resection. In addition, although there are depth limitations due to the absorption and scattering of light in tissue, images acquired using a rat osteoarthritis model also provides insight into the ability to detect targeted fluorescence agents non-invasively. These results suggest that intraoperative resection of tumors detected with both targeted and activatable fluorescent agents is feasible using the new Solaris imaging system.
Citation Format: Jeffrey A. Meganck, Kristine Vasquez, Jeffrey Peterson, Chris Condron, Ali Behrooz, Josh Kempner, Alexandra de Lille, Yiyong Tan, Pete Harvey, Hongyan Gu, Paul Kennedy, Mathew Roxo, Ilias Faqir, Yan Zhang, Leo Mirkin, Peter Miller, Wael Yared. Open air fluorescence imaging of tumors using a new, hands-free translational imaging system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-208. doi:10.1158/1538-7445.AM2015-LB-208