EDB-FN-Targeted Positron Emission Tomography Imaging of Breast Cancer in Mice

Abstract

Abstract Purpose The Breast Imaging Reporting and Data System (BI-RADS) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) positron emission tomography (PET) have some limitations in the diagnosis of breast cancer. The extra domain B splice variant of fibronectin (EDB-FN), which is overexpressed in several cancer types, including breast cancer, is an approved diagnostic and therapeutic target of EDB-FN-positive cancers. Herein, we provide the EDB-FN-targeted peptide EDBp as a noninvasive oncological imaging modality for the molecular imaging of breast cancer.Procedures The binding of the peptide EDBp-Cy5 to EDB-positive breast cancer cells was investigated by flow cytometry and confocal microscopy. Near-Infrared Fluorescence (NIRF) imaging was performed at 48 hours after 1 µmol EDBp-Cy5 was intravenously injected into subcutaneous MDA-MB-231 breast cancer model mice or pulmonary metastasis model mice. Model mice were intravenously injected with approximately 100 µCi of [18F]-EDBp, and PET/CT scanning was performed after 2 hours of in vivo circulation.Results Our results demonstrate that EDBp-Cy5 had a strong binding ability to the MDA-MB-231 cells. EDBp-Cy5 exhibited specific tumor accumulation in MDA-MB-231 subcutaneous and pulmonary metastasis model mice. Importantly, we proposed and validated an EDBp peptide-based radiotracer [18F]-EDBp for PET imaging. [18F]-EDBp provided excellent diagnostic value for PET imaging of breast cancer, especially in subcutaneous tumors. The uptake of [18F]-EDBp in subcutaneous tumors (6.53 ± 0.89%, ID/g) was unexpectedly higher than that in the kidney (4.96 ± 0.20, %ID/g), which is the main metabolic organ of peptides. In the pulmonary metastasis model mice, PET/CT imaging showed that [18F]-EDBp moderately accumulated in the pulmonary metastases.Conclusion The high tumor uptake of this radiotracer in mice suggests its potential for application in PET imaging of EDB-FN-positive breast cancer for disease staging of regional and distant metastases and relapse monitoring.