A great unmet need in oncologic surgery is the ability to accurately identify tumor-positive margins during surgical resections and to rapidly assess the margin status of resection specimens immediately following surgery. While the development of tumor-targeted fluorescent probes is a major area of investigation, it will be several years before these probes are realized for clinical use. We report the use of Indocyanine-green (ICG), a clinically approved, non-targeted dye, in conjunction with fluorescence lifetime detection to provide high accuracy for tumor detection in living mice. The improved performance relies on the distinct fluorescence lifetimes of ICG within tumors compared to tissue autofluorescence, and is further aided by the well-known enhanced permeability and retention of ICG in tumors and the clearance of ICG from normal tissue several hours after intravenous injection. Using in vivo models of human breast and brain tumors, we show that fluorescence lifetime contrast can provide a more than 98% sensitivity and specificity, and a 10-fold reduction in error rates compared to fluorescence intensity. Our studies suggest the significant potential of lifetime-contrast for accurate tumor detection using ICG and other targeted probes under development, both for intra-operative imaging and for ex-vivo margin assessment of surgical specimens
Anand T. Kumar and Stefan Carp, "Fluorescence lifetime-based contrast enhancement of Indocyanine green-labelled tumors (Conference Presentation)," Proc. SPIE 10478, Molecular-Guided Surgery: Molecules, Devices, and Applications IV, 104780A (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2290904.5751479165001.
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