Fluorescence lifetime as a universal marker of solid tumors following injection of indocyanine green: First-in-human results

Abstract

The ability to precisely label and visualize tumors in tissues can improve the accuracy of surgical resections compared to standard of care, which relies on visual inspection and palpation. While fluorescence intensity-based imaging is being evaluated for surgical guidance, variable tumor uptake and incomplete clearance of fluorescent probes reduces tumor vs. normal classification accuracy. Here we demonstrate that the fluorescence lifetime (FLT) of multiple types of solid tumors is longer than the FLT of healthy tissues in patients systemically injected with indocyanine green (ICG), an FDA approved near infrared dye. We show that this cancer-specific lifetime shift can distinguish tumor from normal tissue both at a cellular level using microscopy and in large specimens using wide-field imaging, with an accuracy of over 97% across multiple patients. Unlike intensity, which is a system-specific parameter that depends on tumor dye uptake and depth in tissue, FLT is a system-independent photophysical property that can be quantified in thick tissues. Our study suggests that FLT imaging with ICG can be immediately used to improve the accuracy of cancer surgeries.