Survival of ovarian cancer patients is directly related to the amount of residual disease present after debulking surgery. In 80% of the cases, extensive microscopic cancer remains even after the patient is deemed optimally debulked. Hence, detection of sub-mm cancer clusters during tumor excision is a critical unmet need. Recent studies have shown that reducing the dimensions of residual cancer to less than 1 mm significantly improves clinical outcomes. In the present study we evaluate the performance of a fluorescent, molecular imaging agent, LUM015 (Lumicell, Wellesley, MA), which is activated by cathepsin enzymes in the tumor, and a wide-field-of-view imaging device (Lumicell) to detect sub-mm residual cancer clusters in an mouse model for ovarian cancer.

In this study, we generated orthotopic ovarian cancer mouse models(n=10) with well characterized serous ovarian cancer cell lines, CP70 and SKOV3. Once the tumor disseminated, the imaging agent LUM015 (3.52 mg/kg) was injected via the tail vein, and after 6 hours, the mice were euthanized. Tumor debulking was performed throughout the abdominal cavity. After debulking, the whole abdominal wall was dissected in 4 quadrants, organs were harvested and all were imaged with the LUM device. Features exhibiting high fluorescence were marked and dissected, prepared into slides, and stained with hematoxylin and eosin for pathologic correlation with LUM015 fluorescence imaging.

In 36 tissues from orthotopic ovarian cancer mouse models, LUM015 imaging system could detect the tumor presence with 100% of sensitivity and 60% of specificity. We demonstrated that the imaging system can detect sub-mm cancer clusters that could not be identified with visual inspection.

With a cathepsin activated fluorescence imaging molecule (LUM015) and a wide-field-of-view imaging device, we detected microscopic residual ovarian cancer tumors in orthotopic xenograft models after debulking grossly with high sensitivity. Translation of this imaging technology into the clinical setting may help to detect microscopic residual tumor features during the debulking operation in ovarian cancer.

Citation Format: Youngjeong Na, Tim Kwok, Christopher Awtrey, David B. Strasfeld, Jorge M. Ferrer, David Lee, Michael J. Birrer. Identification of microscopic ovarian tumor foci utilizing a novel imaging device in a murine ovarian cancer model, an opportunity to improve optimal cytoreduction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2056. doi:10.1158/1538-7445.AM2014-2056