Ovarian epithelial cancer is the fifth leading cause of cancer death among women in the US, and has the highest fatality-to-case ratio of all gynecological cancers. Ovarian cancer is especially dangerous due to its propensity to rapidly metastasize, as the disease invades tissues throughout the abdomen by exfoliating from the original tumor. 90% of all ovarian cancer fatalities arise from this occult metastatic disease, which often is composed of a multitude of micrometastases that are exceedingly difficult to detect. While white-light and fluorescence endoscopy have been used, their selectivity and sensitivity have been too limited to accurately detect the microscopic, deadly metastases without high false-positive and false-negative rates. Without the ability to detect this sub-clinical disease state, many women miss a critical period where alternative chemotherapy or radiation treatment might be lifesaving. It is the long-term goal of this project to improve the dismal survival rates (<30%) of ovarian cancer by building, testing, and deploying a sensitive new paradigm for micrometastases detection. In the first aim, this proposal combines the visualization of suspect tumors in situ by fluorescence with the structurally sensitive optical coherence tomography (OCT) imaging technology to provide a selective, sensitive, and fully quantitative microscopic imaging probe for ovarian cancer diagnostics. By utilizing the fluorescence detection for rapid examination and OCT for 3D structural imaging, this in situ probe will not only visualize a tumor, but also render its underlying tissue structure, size, and vasculature. This approach will be realized as a microendoscope composed of tens of thousands of individual image elements that are scanned proximally to ensure a small distal form factor for minimally invasive imaging. In the second specific aim, three-dimensional tumor models and ex vivo tissues will be used for extensive characterization and cataloging so that the multimodal contrast can be used for in situ diagnosis of occult metastatic disease in any tissue. These experiments will find immediate use in the third aim, where the microendoscope will be used in situ to assess micrometastases treatment effectiveness in a mouse model of disseminated ovarian cancer for two treatment regimens. One experiment will study the effectiveness of the chemotherapy Adriamycin, while a second approach will use photodynamic therapy, where photosensitizers are used to generate cytotoxic species for tumor destruction.

Public Health Relevance

This project proposes the construction of a new microscopic fiber probe for the selective detection of deadly ovarian cancer metastatic tumors. By detecting these metastases, this research aims to vastly improve the detection and subsequent treatment of ovarian cancer to save the lives of women with this disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F15-N (20))
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Jakowlew, Sonia B
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Massachusetts General Hospital
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Evans, Conor L; Abu-Yousif, Adnan O; Park, Yong Jin et al. (2011) Killing hypoxic cell populations in a 3D tumor model with EtNBS-PDT. PLoS One 6:e23434
Rizvi, Imran; Celli, Jonathan P; Evans, Conor L et al. (2010) Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer. Cancer Res 70:9319-28
Celli, Jonathan P; Rizvi, Imran; Evans, Conor L et al. (2010) Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model. J Biomed Opt 15:051603