Abstract 4340: Development of short peptide probe to detect ovarian tumors in mouse xenograph model

Abstract

Abstract Ovarian cancer is the leading gynecological cancer in women with five year survival rate less than 45%. Ovarian epithelial cancer (OEC) is responsible for 80 to 90% of all ovarian cancers. Postmenopausal women have high level of gonadotropin in blood circulation and high occurrence of OEC. Therefore, the elevated gonadotropin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), was proposed to contribute to transforming normal ovarian surface epithelium to neoplastic ovarian surface epithelium. The studies on gonadotropin theory have shown both supporting and conflicting epidemiological and animal model data. Therefore an alternative marker for ovarian tumor detection is beneficial. Follicule Stimulating Hormone Receptor (FSHR) belongs to G protein-coupled receptor with substantial extracellular domains. FSHR normally is expressed on normal ovarian epithelium, fallopian tubal epithelium and similar to LHR. Recent studies showed that FSHR is not only highly expressed on many ovarian cancer cells but is involved in the development and progression of ovarian cancer influencing a variety of oncogenes (MAPK, EGFR, c-myc, and HER-2/neu). FSHR expression increases in the following order: ovarian epithelial inclusions (OEIs) to benigh ovarian epithelial tumor (OET), and to borderline OETs. Our objective is to develop a small molecular weight ligand to image in vivo the differential expression of FSHR associated with OEC, possibility to image OEC in different stages with associated binding molecules to FSHR. D.W. Lee et. al. identified a deca peptide (BI-10) from FSH binding inhibitor of bovine serum. We conjugated the BI-10 peptide with fluorescein to quantify the binding affinity of OVCAR3 cells in flow cytometry. The cells were incubated with BI-10 at various concentrations for 30 mins before removing from six-well culture plates and washing off free peptides. The EC50 of BI-10 binding peptides to OVCAR3 was measured to be 160 μM, with an average number of FSHR receptors per cell to be 1.7×107. After conjugating a NIR fluorochrome (Alexa Fluoro 750) to this peptide and and injection (i.v.) into a mouse xenograft model of ovarian cancer, OEC tumors were clearly detected by optical imaging. A tumor-to-reference tissue update ratio was measured to be 1.20, 1.26, and 1.43 with respect to injected dose 15, 30, and 120 μg probe, respectively. We are currently testing techniques to further increase the BI-10 peptide binding to various ovarian cancer cell lines both in vitro and in vivo by constructing multimeric forms including the BI-10 peptide with various flexible linkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4340.