# Dual function theranostic constructs for photoacoustic guided surgery and photodynamic therapy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $617,122

## Abstract

PROJECT SUMMARY: Survival rates in patients with oral cavity tumors have remained nearly stagnant in the
past decade with exceptional morbidity e.g., tongue cancers. The goal of this Academic-Industry Partnership
(AIP) application is to develop, for the first time, a single theranostic agent namely targeted Dual Function
Antibody Conjugate (DFAC) amenable to deep tissue photoacoustic imaging (PAI) with targeted photodynamic
therapy (PDT), and an integrated PAI-ultrasound imaging (USI) module for surgery guidance such that the two
main barriers to oral cancer treatment outcomes are overcome. Difficulty in gauging the depth of tumor invasion
during surgical resection and residual microscopic disease are the two main barriers responsible for the high
loco-regional recurrence rates in oral cavity tumors. Cautionary removal of extra normal tissue leads to functional
loss and a compromised quality of life. Through this AIP, we establish a collaborative framework between the
academic research lab of Dr. Hasan at Massachusetts General Hospital (MGH), the clinical Otolaryngology
surgical team of Drs. Varvares and August at Mass Eye and Ear Infirmary and MGH, and the Akita Innovations
industry team, to create a comprehensive theranostic solution that enables deep tissue image-guided, normal
tissue-sparing surgery and tumor-targeted spatially-localized therapy in the oral cavity. Our synergistic scientific
expertise, respective infrastructures, clinical translation experience and geographic proximity position us well to
achieve our goals. The proposal has 3 parts that will enable deep tissue image-guided surgery and treat residual
disease in one intraoperative setting. 1. A DFAC, that enables both imaging and therapy by targeting Epidermal
growth factor receptor (EGFR), an established biomarker in oral cavity tumors, 2. A custom-built, PAI integrated
clinical USI module for surgical guidance. 3. Targeted PDT. DFAC is composed of cetuximab, an FDA-approved
EGFR targeting antibody, conjugated to a new near-infrared (>850 nm) napthalocyanine dye for deep-tissue PAI
and an FDA-approved photosensitizer Benzoporphyrin Derivative (BPD). We postulate that DFAC-enabled
deep-tissue PAI- guided surgery and intraoperative PDT of residual disease will achieve local tumor control,
reduce recurrence, increase disease-free survival and improve quality of life in oral cancer patients. The concept
will be validated pre-clinically and clinically in 4 specific aims: Aim-1 Development and in vitro optimization of
DFACs for photoacoustic contrast and therapeutic efficacy. Optimize clinical intra-oral USI systems to PAI via
customized light delivery strategies and spectroscopic algorithms. Aim-2. Perform rodent toxicology studies,
GMP production of DFAC and obtain eIND approvals. Aim-3. Evaluation of therapeutic efficacy in mouse models
of oral cancer. Aim-4. Implementation of first-in-human Phase 0 clinical trial with DFAC-guided PAI ability to
delineate deep tumor margins. Rele...

## Key facts

- **NIH application ID:** 9857582
- **Project number:** 5R01CA231606-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tayyaba Hasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $617,122
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857582

## Citation

> US National Institutes of Health, RePORTER application 9857582, Dual function theranostic constructs for photoacoustic guided surgery and photodynamic therapy (5R01CA231606-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857582. Licensed CC0.

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