Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients

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 intensitybased 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.

Recent Advances in NIR-II Materials for Biomedical Applications

“…In 2023, FDA approved ICG has been reported for wide field fluorescence lifetime imaging to distinguish tumor tissue and normal tissue. 36 The nanosecond scaled fluorescence lifetime will benefit the rapid lifetime collection, providing possibility for real-time and dynamic fluorescence lifetime imaging for lifetime image-guided surgery. On the basis of these efforts, it is also a good choice to endow lifetime probes with both diagnosis and therapy function to observe therapy induced physiological changes under the guidance of fluorescence/ luminescence lifetime imaging, optimizing the personalized therapeutic protocols.…”

“…While compared to the inorganic nanoparticles with slow clearance and unpredictable pharmacokinetics, organic molecular dyes have more promising prospects, especially for the future clinical translation. In 2023, FDA approved ICG has been reported for wide field fluorescence lifetime imaging to distinguish tumor tissue and normal tissue . The nanosecond scaled fluorescence lifetime will benefit the rapid lifetime collection, providing possibility for real-time and dynamic fluorescence lifetime imaging for lifetime image-guided surgery.…”

“…Image-guided surgery contains multiplexed image-guided surgery, reproduced with permission from ref . Copyright 2020 John Wiley & Sons; indocyanine green (ICG) for the first-in-human liver-tumor image-guided surgery; and ICG for fluorescence lifetime image-guided surgery . TME visualization consists of fluorescence intensity-based visualization, reproduced with permission from ref .…”

CORR Insights®: Do Patients Treated With an Unplanned Resection for Small Superficial Soft Tissue Sarcomas Have Worse Long-term Survival Than Those Initially Treated With an Oncologic Resection?

“…The evolution of lifetime indocyanine green (ICG) fluorescence and other intraoperative techniques utilizing alternative probes for visualizing tumor tissue is ongoing [8]. Anticipating a future in which surgeons can efficiently identify malignant tissue and cells and achieve reliable negative margins in surgical resections holds real promise.…”

“…Ideally, the integration of handheld devices or glasses could facilitate this transformative capability. Promisingly, Pal et al [8] have reported on ICG half-life and its ability to discriminate between benign and malignant cells in different subhistologies of sarcomas and carcinomas. Independent of the tumor histology, Pal et al [8] were able to differentiate between benign and malignant cells with an accuracy of 99% when analyzing based on the cellular half-life of ICG.…”