In Vivo Detection of Breast Cancer Growth Factor Receptors via Photoacoustic Imaging and Fiber-Optic Fluorescence Sensing

Bustamante, Gilbert
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New breast cancer treatments now include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, photoacoustic imaging and fluorescence sensing by a fiber-optic probe were utilized to characterize HER2 and EGFR overexpressed tumors in vivo. A novel filtered-backprojection algorithm with a unique weighting function for photoacoustic image reconstruction was created to reconstruct images of high quality at different conditions. The algorithm was able to handle intense geometric imbalances and limited detection points to reconstruct images with needed resolution for diagnostics. In conjunction, HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates for photoacoustic imaging and fluorescence sensing. Photoacoustic images of the tumors were rendered with the novel weighted algorithm to view conjugate accumulation at the tumor sites. Fiber-optic fluorescence sensing was used to distinguish between tumor types through fluorescence intensity, with fluorophore concentrations detectable at levels as low as 15 nM. The presented system offers a minimally invasive approach to characterize the molecular signatures of breast cancer in vivo.

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Breast cancer, EGFR, Fiber-optic probe, Fluorescence, HER2, Photoacoustic
Biomedical Engineering