Despite significant advances in the treatment of ovarian cancer (OC), patients with recurrent metastatic malignancies still have poor outcomes, and most of these patients will experience disease relapse. For advanced or metastatic OC disease, platinum-based chemotherapy remains the primary backbone for systemic treatment. Unfortunately, platinum-resistant OC occur in about 20% of patients after first-line platinum-based chemotherapy. To address this problem, mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate (ADC) comprising a folate receptor alpha (FRa)-binding antibody, was recently granted FDA approval for patients suffering from platinum-resistant disease with high FRa expre...

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Despite significant advances in the treatment of ovarian cancer (OC), patients with recurrent metastatic malignancies still have poor outcomes, and most of these patients will experience disease relapse. For advanced or metastatic OC disease, platinum-based chemotherapy remains the primary backbone for systemic treatment. Unfortunately, platinum-resistant OC occur in about 20% of patients after first-line platinum-based chemotherapy. To address this problem, mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate (ADC) comprising a folate receptor alpha (FRa)-binding antibody, was recently granted FDA approval for patients suffering from platinum-resistant disease with high FRa expression. However, current methods are limited in their ability to measure FRa expression of a tumor volumetrically, longitudinally, and in situ. Thus, there is a dire clinical need for a non-invasive modality that can predict and monitor ADC therapy response to allow for timely modifications to one's treatment plan. Recently, photoacoustic-ultrasonic (PA-US) imaging has emerged as a promising modality that is capable of visualizing molecularly targeted contrast agents at depth (up to ~5 cm) and with high contrast and resolution. Our hypothesis is that PA-US imaging using FRa-targeted polymersomes loaded with highly concentrated indocyanine green (ICG) dye (Ps-JICG) can provide quantitative, longitudinal, and point-of-care monitoring and prediction of IMGN853 response for OC. Our preliminary data show that targeted Ps-JICG provides impressive stability, linearity, PA-signal intensity, and molecular targeting specificity. All constitutive components of the agent are FDA approved, leading to a straightforward path towards clinical translation. Upon successful completion of these studies, we will provide the foundation for development of ADC-therapy planning and monitoring with molecular and functional PA-US imaging in clinical settings.

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