# Hedgehog Pathway Activity and Targeting in KCOT

> **NIH NIH R00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $69,400

## Abstract

Abstract
Odontogenic neoplasms, including ameloblastomas and keratocystic odontogenic tumors, demonstrate locally aggressive
and destructive behavior. A variety of surgical treatments may be used for these neoplasms; however, their location makes
complete resection difficult, leading to residual disease and high rates of recurrence. While over-aggressive resection may
be carried out to reduce residual disease, this results in greater disfiguration and reduced facial function for the patient. Our
work on these tumors has focused on understanding their genetics, examining new therapies, and developing new models.
At present, there are currently no biomarkers used for these tumor types, and no diagnostic strategies beyond standard
biopsy. The ability to accurately assess tumor margins with specific, non-invasive imaging could result in the preservation
of healthy tissue and improvements in long-term local tumor control. We hypothesize that epidermal growth factor receptor
(EGFR) expression in aggressive odontogenic neoplasms may be used to specifically visualize tumors intraosseously,
which may allow the tumor margins to be assessed intraoperatively. Our approach utilizes FDA-approved fluorescent and
radiolabeled epidermal growth factor (EGFR) antibodies and imaging technology. We aim to establish the clinical validity of
using panitumumab as an imaging agent for ameloblastomas. The long-term goal of our studies is to implement non-invasive
biomarker-based imaging of ameloblastomas in clinical care, making it possible to precisely label tumor tissue and assess
tumor margins either pre- or intraoperatively, allowing clinicians to provide better care for their patients. The objective of our
current studies is to determine the sensitivity and specificity of labeled anti-EGFR antibodies to image ameloblastoma tissue
using in vivo preclinical models. Two hypothesis-driven specific aims will be investigated as follows: (1) To determine the in
vivo sensitivity and specificity of panitumumab-IRDye800 for human ameloblastoma patient-derived xenografts (PDX). We
hypothesize that panitumumab-IRDye800 will localize to ameloblastoma tumor tissue significantly more than a non-specific
IgG-IRDye800 antibody and that the fluorescence will be higher than the background fluorescence of normal tissue. (2) To
determine the clinical validity of panitumumab-IRDye800 and 89Zr-panitumumab for the surgical removal of tumors using an
intraosseous mandibular model of ameloblastoma. We hypothesize that both panitumumab-IRDye800 and 89Zr-
panitumumab will localize to ameloblastoma cells and allow accurate margin determination and surgical removal of tumors.
This project has the potential to develop a method to accurately image ameloblastomas and provide a tool for assessing
bone invasion in a patient population that is vastly under-represented in the existing research. During the K99 and R00
portions of this grant, we have created patient-derived xenograft mouse models of amelo...

## Key facts

- **NIH application ID:** 10106028
- **Project number:** 3R00DE023826-05S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Hope Amm
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,400
- **Award type:** 3
- **Project period:** 2020-07-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106028

## Citation

> US National Institutes of Health, RePORTER application 10106028, Hedgehog Pathway Activity and Targeting in KCOT (3R00DE023826-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10106028. Licensed CC0.

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