Image-Guided Phototherapy to Prevent Ovarian Cancer Recurrence

Project Number: U54 EB015403 (Klapperich)
Sponsor: NIH (through Boston University)
Award Period: 07/01/2015–06/30/2016

Abstract: This proposal aims to reduce the high rate of ovarian cancer (OvCa) recurrence and mortality by monitoring and selectively destroying residual, microscopic tumors using a “theranostic” platform that integrates fluorescence microendoscopy and near infrared phototherapy. Patients are presently subjected to a morbid treatment regimen consisting of surgical tumor debulking and high-dose-intensity chemotherapy. Here we propose a paradigm shift towards image guided treatment of the microscopic residual disease following surgery with staggered tumor targeted, activatable phototherapy and low dose chemotherapy on an as-needed basis. The targeted and activatable phototherapy synergizes with chemotherapy to enable enhanced treatment efficacy per cycle by reversing cancer cell drug-resistance. For instance, a single cycle of activatable phototherapy plus chemotherapy achieves 97% killing of disseminated micrometastases versus 3% for chemotherapy alone (PNAS 111, E933–42, 2014). This approach not only offers great promise to improve patient survival and quality of life but also has potential to relax the intensity of the conventional chemotherapy drug infusion schedule, which is often compromised by the need for dose interruptions due to toxicity, patient compliance and socioeconomic barriers to transportation for frequent hospital visits.

In its present form, the platform accomplishes image-guided treatment with reduced toxicity and potentiation of chemotherapy in a preclinical mouse model of micrometastatic OvCa (PNAS 111, E933–42, 2014; featured in an editorial as “ready for translation”: Sci Transl Med 6, 229ec54, 2014). However, the imaging component requires extensive and tedious calibrations to remove background and offline processing (Supplementary Fig. S2 in PNAS 111, E933–42, 2014), which precludes real-time decision-making in the clinic. These limitations are overcome by the next generation fluorescence microendoscope proposed here. During the one-year funding period, this grant aims to validate the next generation fluorescence microendoscope that enables real-time imaging and analysis for sensitive detection of micrometastases—a major step towards clinical translation of this platform for image-guided treatment of residual OvCa.