# Small Molecule Probes for Fluorescence-guided Head and Neck Cancer Surgery

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $231,000

## Abstract

PROJECT SUMMARY
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer type, with over 650,000
cases diagnosed annually worldwide. Positive margins are reported in up to 30% of head and neck cancer sur-
geries, where margin status is a major prognostic factor for overall survival. While preoperative x-ray, computed
tomography (CT) and ultrasound imaging have enabled in depth evaluation, diagnosis, and surgical planning, a
gap continues to exists between preoperative imaging and intraoperative reality. Accurate surgical identification
of the tumor margins and small lesions remains challenging. Surprisingly, no clinically approved technology can
directly enhance intraoperative guidance for tumor resection and tis-sue preservation for head and neck cancers,
which are typically performed through anatomical knowledge, visual cues and palpation. Fluorescence Guided
Surgery (FGS) has successfully integrated into clinical medicine with only two FDA-approved near-infrared (NIR,
650-900 nm) fluorophores. FGS systems operate almost exclusively in the NIR region, where tissue chromo-
phore absorbance, autofluorescence and scatter fall to local minima, permitting high contrast and high-resolution
imaging at depths up to a centimeter. Intraoperative guidance with tumor-specific FGS could significantly improve
surgical outcomes for head and neck cancer patients, providing a new paradigm for surgery. An important con-
sideration for wide clinical adoption is ease of implementation into the current surgical workflow. Presently, the
majority of FGS contrast agents under development are classified as “always-on” probes, where continuous
fluorescence emission occurs throughout imaging, regardless of the probe proximity to its binding target. Off-
target accumulation of these always-on probes leads to elevated background signal, and a considerable amount
of time is required for the non-specific probe accumulation to be cleared to generate adequate tumor-to-back-
ground ratio (TBR) for decision-making during the surgery. Patients are required to receive contrast agent injec-
tion days before surgery. For patients, this implicates additional hospital visits with extra costs and stress. This
is in part due to large probe size resulting in limited extravasation, long circulation times, and impaired tumor
penetration. To alleviate these challenges, smaller targeting moieties with high specificity and affinity are highly
desirable to provide superior TBR shortly after systemic administration, permitting ready integration into the ex-
isting surgical workflow. Herein, we propose to develop a novel tumor-targeted FGS solution to address this
unmet clinical need. We will develop first-in-class NIR fluorogenic probes that target mutants of EGFR in head
and neck cancer, where high TBR will be crucial for accurate tumor margin assessment, the detection of small
tumor nodules, residue lesions and multi-focal disease. These novel fluorogenic probes as int...

## Key facts

- **NIH application ID:** 10829482
- **Project number:** 5R21EB034340-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Lei Garrett Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,000
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829482

## Citation

> US National Institutes of Health, RePORTER application 10829482, Small Molecule Probes for Fluorescence-guided Head and Neck Cancer Surgery (5R21EB034340-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829482. Licensed CC0.

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