Close to 40,000 Americans will be diagnosed with triple-negative breast cancer (TNBC) in 2018, a subtype of invasive breast cancer with a poor prognosis. Patients with TNBC are preferably treated with neoadjuvant chemotherapy (NAC), which results in ~50% of patients having either pathologic compete response (pCR) or minimal residual disease upon resection. However, not all patients have a substantial response to NAC, and thus there is a dire clinical need for a non-invasive modality that is capable of monitoring therapy response to allow for timely modifications to one’s treatment plan or to assess the degree/location of residual disease. Recently, photoacoustic-ultrasonic (PA-US) imaging ha...

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Close to 40,000 Americans will be diagnosed with triple-negative breast cancer (TNBC) in 2018, a subtype of invasive breast cancer with a poor prognosis. Patients with TNBC are preferably treated with neoadjuvant chemotherapy (NAC), which results in ~50% of patients having either pathologic compete response (pCR) or minimal residual disease upon resection. However, not all patients have a substantial response to NAC, and thus there is a dire clinical need for a non-invasive modality that is capable of monitoring therapy response to allow for timely modifications to one’s treatment plan or to assess the degree/location of residual disease. Recently, photoacoustic-ultrasonic (PA-US) imaging has emerged as a promising modality that is capable of non-invasively visualizing molecularly targeted contrast agents at depth (up to ~5 cm) and with high contrast and resolution. Epidermal growth factor receptor (EGFR), which tends to be overexpressed in TNBC, is a promising imaging biomarker because of its demonstrated correlation with TNBC prognosis and predictive value regarding pCR achievement. Our hypothesis is that PA-US imaging using EGFR-targeted liposomes loaded with highly-concentrated indocyanine green (ICG) dye (Lipo-JICG) can provide quantitative, longitudinal, and point-of-care monitoring and prediction of NAC response for TNBC. Our preliminary data show that targeted Lipo-JICG provides impressive stability, linearity, PA-signal intensity, and molecular targeting specificity. The lipids, ICG, and humanized anti-EGFR antibodies needed for our approach are all FDA approved, leading to a straightforward path towards clinical translation. In addition, with MDACC’s recently acquired clinical PA-US imaging system, we have all of the resources to conduct a pilot clinical trial in the near future. Upon successful completion of these studies, we will provide the foundation for development of NAC monitoring with molecular and functional PA-US imaging in clinical settings.

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