Abstract 5259: Non-invasive determination of in vivo myeloperoxidase activity in ovarian cancer mouse model
Authors: Rao V. Papineni, Vinicius Craveiro, John Pizzonia, Jennie Holmberg, Gil Mor
Journal: Cancer Research (2012)

Abstract Myeloperoxidase (MPO) is an inflammatory heme protein present in myeloid cells- neutrophils, microglia, and macrophages. The enzyme activity of MPO utilizes hydrogen peroxide in the process of reactive oxygen species generation. Myeloperoxidase has been suggested recently as a likely marker in ovarian carcinoma. This relationship between the MPO and ovarian cancer however was deduced primarily from data obtained from in vitro studies using cancer cell lines and from immunostaining of ovarian carcinoma paraffin blocks. Therefore, a real-time determination of in vivo MPO activity in the tumor and during the progression of ovarian cancer will be valuable to assess the role of innate immune process in ovarian cancer progression, in cancer treatment, and the proper management of current therapies. Here, we developed non invasive methodologies to determine the MPO activity in intraperitoneal ovarian cancer tumor mouse model. Tri-modal non invasive imaging of the metastatic ovarian cancer in athymic mice model were performed to obtain fluorescence, luminescence, and X-ray images at different time points during the progression of the intraperitoneal tumor metastasis. Progression of the tumor metastasis was monitored using fluorescence; simultaneously MPO activity was obtained by luminescence imaging. The MPO activity was detected by i.p injection of Luminol (5-amino-2,3-dihydro-1,4-phthalazine-dione) in physiological buffered saline (5 mg / 25gm mice). Luminol a redox-sensitive compound emits blue luminescence upon exposure to oxidizing agents, and in vivo, and has been established to have unique specificity to MPO activity. The fluorescence and luminescence images were overlaid on planar X-ray images for anatomical coregistration. The results show a robust increase in MPO activity in the mouse with the tumor development as compared to the control mice of the same cohort. Increase in MPO activity as a result of neutrophil activation was observed in the early phase of the ovarian cancer progression, and this increase subsides in the latter stages. However, the lumiscence signal intensities vary between the tumors, and near negligible MPO activity was observed in some tumors indicating a differential tumor microenvironment within the mouse. Further, the activity is far greater, at least in the initial stages, at the lung, nasal and other distal regions when compared to the intraperitoneal tumors. These real-time monitoring methodologies of MPO activity by in vivo imaging will greatly enhance the understanding of the tumor microenvironment during ovarian cancer progression, and contribute significantly in the development of better cancer treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5259. doi:1538-7445.AM2012-5259