# Fluorescence lifetime-based tumor contrast enhancement using exogenous probes

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $456,031

## Abstract

Imaging techniques that can enhance tumor contrast against non-specific background can
significantly impact diagnostic and surgical applications in oncology. Fluorescence optical imaging is
being evaluated for disease diagnosis and surgical treatment, using probes that either preferentially
accumulate in tumors, or are antibody conjugated to label tumor-specific receptors. While there has
been a significant progress in the development of molecularly targeted near infrared fluorescent
probes, background fluorescence from non-specific probe accumulation remains a major confound
that reduces sensitivity and specificity for tumor detection. Even when the probe clearance is rapid,
tissue autofluorescence can be significant compared to the tumor fluorescence. Existing clinical
optical imaging systems primarily employ fluorescence intensity-based imaging. Fluorescence
intensity strongly depends on tissue attenuation and experimental factors such as excitation light
intensity, and therefore cannot distinguish tumor bound probe from non-specific probe or tissue
autofluorescence on an absolute scale. Our preclinical and clinical studies indicate that the
fluorescence lifetimes of tumor and normal tissue in subjects injected with cancer targeted probes are
distinct and independent of experimental parameters under typical conditions. We have shown that
this FLT contrast dramatically improves the accuracy for tumor vs. normal classification compared to
intensity-based imaging using the FDA-approved near infrared fluorescent dye, Indocyanine green
(ICG). Building on this exciting finding, the goal of this proposal is to robustly validate fluorescence
lifetime as a contrast mechanism for tumor identification in oral cancers using ICG. We will develop a
portable time domain imaging system for concurrent intraoperative imaging and surgical specimen
mapping and optimize the system using preclinical models. Subsequently, we will validate the system
for intraoperative imaging and specimen margin assessment using clinical studies in head and neck
cancer surgery patients systemically injected with ICG, and determine the dosage and injection time
points that provide optimal accuracy for tumor vs normal classification. This proposal will also lead to
future applications of lifetime contrast to enhance accuracy of tumor detection in other cancers, using
ICG and novel cancer targeted probes currently under development.

## Key facts

- **NIH application ID:** 10931674
- **Project number:** 5R01DE033427-03
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Anand T.N. Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $456,031
- **Award type:** 5
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931674

## Citation

> US National Institutes of Health, RePORTER application 10931674, Fluorescence lifetime-based tumor contrast enhancement using exogenous probes (5R01DE033427-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931674. Licensed CC0.

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