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Updated: Jul 7, 2025
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence
Samuel S Streeter1,2, Xiaochun Xu3, Kendra A Hebert3
1Department of Orthopaedics, Dartmouth Health, One Medical Center Drive, Lebanon, NH, 03756, USA. samuel.stewart.streeter@dartmouth.edu.
Purpose:
ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for fluorescence-guided surgery of sarcomas. To date, studies using ABY-029 have occurred in tumors naïve to chemotherapy (CTx) and radiation therapy (RTx), although these neoadjuvant therapies are frequently used for sarcoma treatment in humans. The goal of this study was to evaluate the impact of CTx and RTx on tumor EGFR expression and ABY-029 fluorescence of human soft-tissue sarcoma xenografts in a murine model.
Procedures:
Immunodeficient mice (n = 98) were divided into five sarcoma xenograft groups and three treatment groups - CTx only, RTx only, and CTx followed by RTx, plus controls. Four hours post-injection of ABY-029, animals were sacrificed followed by immediate fluorescence imaging of ex vivo adipose, muscle, nerve, and tumor tissues. Histological hematoxylin and eosin staining confirmed tumor type, and immunohistochemistry staining determined EGFR, cluster of differentiation 31 (CD31), and smooth muscle actin (SMA) expression levels. Correlation analysis (Pearson's correlation coefficients, r) and linear regression (unstandardized coefficient estimates, B) were used to determine statistical relationships in molecular expression and tissue fluorescence between xenografts and treatment groups.
Results:
Neoadjuvant therapies had no broad impact on EGFR expression (|B|≤ 7.0, p ≥ 0.4) or on mean tissue fluorescence (any tissue type, (|B|≤ 2329.0, p ≥ 0.1). Mean tumor fluorescence was significantly related to EGFR expression (r = 0.26, p = 0.01), as expected.
Conclusion:
Results suggest that ABY-029 as an EGFR-targeted, fluorescent probe is not negatively impacted by neoadjuvant soft-tissue sarcoma therapies, although validation in humans is required.
Insights
Neoadjuvant therapies do not negatively affect ABY-029 fluorescence in soft-tissue sarcoma xenografts. This epidermal growth factor receptor (EGFR)-targeted probe remains a viable option for fluorescence-guided surgery, pending human trials.
Area of Science:
- Oncology
- Molecular Imaging
- Surgical Oncology
Background:
- ABY-029 is an epidermal growth factor receptor (EGFR)-targeted Affibody peptide with near-infrared fluorescence, investigated for fluorescence-guided sarcoma surgery.
- Previous studies utilized ABY-029 in treatment-naïve tumors, but neoadjuvant chemotherapy (CTx) and radiation therapy (RTx) are common in human sarcoma treatment.
- The impact of neoadjuvant therapies on EGFR expression and ABY-029 fluorescence in soft-tissue sarcomas was previously unevaluated.
Purpose of the Study:
- To assess the effect of neoadjuvant chemotherapy (CTx) and radiation therapy (RTx) on epidermal growth factor receptor (EGFR) expression.
- To evaluate the impact of CTx and RTx on the fluorescence of ABY-029, an EGFR-targeted imaging probe.
- To determine the suitability of ABY-029 for fluorescence-guided surgery in soft-tissue sarcomas that have undergone neoadjuvant treatment.
Main Methods:
- Ninety-eight immunodeficient mice with soft-tissue sarcoma xenografts were assigned to control, CTx only, RTx only, or CTx followed by RTx groups.
- Following ABY-029 injection, ex vivo fluorescence imaging was performed on various tissues, including tumors.
- Immunohistochemistry was used to quantify EGFR, CD31, and SMA expression, with statistical analyses correlating molecular expression and fluorescence.
Main Results:
- Neoadjuvant therapies did not significantly alter EGFR expression levels across xenografts.
- Mean tissue fluorescence, including tumor fluorescence, was not broadly impacted by CTx or RTx.
- A significant positive correlation was observed between tumor fluorescence and EGFR expression (r=0.26, p=0.01).
Conclusions:
- The study suggests that neoadjuvant therapies (CTx and RTx) do not adversely affect the performance of ABY-029 as an EGFR-targeted fluorescent probe.
- ABY-029 fluorescence is correlated with EGFR expression, supporting its potential as a biomarker.
- These findings indicate ABY-029's potential utility in fluorescence-guided surgery for soft-tissue sarcomas, even after neoadjuvant treatment, although human validation is necessary.
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