Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model
Tobias Bäuerle1, Suresh Gupta1, Shaokuan Zheng1
1From the Institute of Radiology, Friedrich-Alexander University of Erlangen-Nurnberg, Erlangen, Germany (T.B., L.S.); Laboratory of Molecular Imaging Probes, Department of Radiology (S.G., A.L., A.B.), and Advanced MRI Center and New England Center for Stroke Research, Department of Radiology (S.Z., M.M.), University of Massachusetts Medical School, 55 Lake Ave North, S6-434, Worcester, MA 01655; Department of Nuclear Medicine, Friedrich-Alexander University of Erlangen-Nurnberg, Germany (S.M., O.P.); A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Mass (P.C.); and A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation (A.B.).
Multimodality imaging accurately measured epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) bone metastases. This approach offers a comprehensive assessment of EGFR overexpression in metastatic TNBC models.
Area of Science:
- Oncology
- Molecular Imaging
- Biomedical Engineering
Background:
- Triple-negative breast cancer (TNBC) bone metastases present challenges for targeted therapy due to molecular marker heterogeneity.
- Epidermal growth factor receptor (EGFR) is a potential therapeutic target and marker in TNBC metastasis.
- Accurate measurement of EGFR expression is crucial for guiding treatment strategies in metastatic TNBC.
Purpose of the Study:
- To develop and validate multimodality imaging techniques for quantifying EGFR expression in TNBC bone metastases.
- To assess EGFR as a therapy-relevant and metastasis-associated molecular marker in an orthotopic TNBC model.
- To correlate imaging findings with molecular analyses for comprehensive EGFR assessment.
Main Methods:
- An orthotopic bone metastasis model of EGFR-positive TNBC was established in rats (n=22).
- Multimodality imaging including bioluminescence imaging, SPECT/CT, PET/CT, and MRI was employed.
- Receptor-specific MRI and PET/CT utilized anti-EGFR F(ab')2 fragments conjugated with imaging substrates (Gd-5HT-DOTAGA, Ga-68-5HT-DOTAGA). EGFR expression was validated via RT-qPCR and immunohistochemistry.
Main Results:
- Both osteolytic and nonosteolytic TNBC tumors exhibited significantly higher MRI signal enhancement compared to normal bone marrow (3-6 fold increase, P < .01).
- Micro PET/CT revealed heterogeneous EGFR expression, correlating with regional MRI signal intensity elevations (P < .001).
- Molecular analyses confirmed high EGFR protein and mRNA expression in invasive tumor regions, corroborating imaging results.
Conclusions:
- Multimodal molecular receptor imaging provides a comprehensive assessment of EGFR overexpression in an orthotopic TNBC bone metastasis model.
- The developed imaging techniques are capable of detecting and quantifying therapy-relevant molecular markers in metastatic cancer.
- This approach holds promise for personalized treatment strategies in patients with metastatic TNBC.
