Pre-operative Paired Agent Assessment for Cytoreduction of Epithelial Ovarian Cancer - PROJECT SUMMARY Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer, accounting for 90% of diagnosed cases.6 The standard of care for EOC involves cytoreductive surgery (CRS) to remove as many lesions as possible, or to “debulk” the cancer, followed by chemotherapy. The success rate of CRS is highly variable (25% to 90%) because not all patients are ideal candidates for CRS.1-4 Consequently, non-ideal patients receive suboptimal treatment, which incurs the need for additional procedures, and increases both morbidity and cost. Predicting the success rate of CRS in patients is challenging due to limited screening techniques for assessing the spread of cancer.4,6 Cytalux (pafolacianine, OTL38) is clinically approved for intraoperative guidance of ovarian cancer, but its diagnostic ability is limited by off-site binding in lymph nodes and non-specific background, and it has not been used for preoperative screening.18,19 To overcome this limitation, we aim to develop a novel fluorescence pre-operative screening tool to assess the tumor burden and guide CRS treatment planning. To accomplish this goal, we will develop a novel, minimally invasive laparoscopic paired-agent imaging (PAI) workflow to determine the degree of cancer metastases in EOC. PAI is a molecular fluorescence imaging technique that enhances contrast between cancerous and normal tissue by ratioing the signal from tumor- targeted and non-specific fluorescence probes, thus reducing off-site and non-specific fluorescence. The first aim is to identify a targeted and an untargeted fluorescent agent pair for specifically targeting folate receptor-𝛼 (FR-𝛼) ovarian cancers. We will study the pharmacokinetic and diagnostic accuracy of three targeted (OTL38, mirvetuximab, and a novel anti-FR𝛼 scFv) and untargeted agent pairs to determine the optimal pair with the highest diagnostic performance for identifying lesions. Additionally, the three pairs will be of varying molecular size to examine its impact on clearance, binding affinity, and diagnostic accuracy. The second aim is to develop an integrated dual channel fluorescent laparoscope for in vivo imaging and diagnosis of EOC. The laparoscopic system will be tested and characterized using optical phantoms and in vivo EOC mouse models. The proposed training plan is sponsored by Dr. Kimberley Samkoe, an expert in quantitative fluorescence molecular imaging and experience in translational imaging methodologies. The overall goal of the training plan is to provide the PI, Sanjana Pannem, with foundational skills for pursuing a career in the biomedical industry. The fellowship training plan involves gaining clinical knowledge of the ovarian cancer workflow (Dr. Wilkinson- Ryan), optical imaging system development (Dr. Elliott), development of targeted proteins, (Dr. Ackerman), the selection of imaging agents for clinical translation (Dr. Samkoe), and broadening expertise in software development for visualizing and analyzing fluorescence images (Dr. Paulsen). Additionally, professional skills will be developed through mentorship, attendance of scientific conferences in the biomedical imaging and ovarian cancer fields, and participation in accelerators to gain entrepreneurial experience.
