Abstract 5310: Positron emission tomography imaging of endometrial cancer using an anti-EMP2 minibody

Abstract

Abstract Endometrial cancer is increasingly affecting pre-menopausal women, prompting a need to develop fertility-sparing therapy, and monitor response to treatment by quantitative non-invasive strategies. Epithelial membrane protein 2 (EMP2) is a tetraspan protein associated with surface localization and function of cancer-relevant integrin isoforms, and EMP2 expression in endometrial cancer correlates with increasing cancer stage and poor prognosis. As EMP2 is highly expressed in endometrial cancer, this pre-clinical study tested the feasibility of non-invasive detection of human endometrial tumor xenografts using a radiolabeled anti-EMP2 diabody and positron emission tomography (PET). EMP2 biodistribution in murine organ was determined by western blot and immunohistochemistry. Anti-EMP2 minibody (MB83) fragment was designed and transfected into CHO-K1 cells. Purified minibody was DOTA conjugated and the binding activity was tested by flow cytometry using endometrial cancer cell line, Hec-1A/EMP2 cells. Then conjugated minibody was chelated with Cu-64. In vivo biodistribution of Cu-64 labeled MB83 in Balb/c nu/nu mice were determined by microPET imaging and AMIDE sofeware. MB83 location was determined by microPET in mice bearing Hec1a/EMP2 xenograft. EMP2 expression was detectable in the lung but not other organs by either western or immunohistochemistry. The absence of detectable EMP2 protein in the organs reflects that the target tumor with high EMP2 protein could uptake anti-EMP2 antibody which could be observed by microPET. The specific uptake of MB83 minibody within the Hec1a/EMP2 tumor can be seen both visually and quantitatively. Selective tumor uptake became more specific over time. In contrast, 2-deoxy-2-[18F]fluoro-D- glucose (FDG) microPET uptake by HEC-1A/EMP2 was minimal, reflecting the poor detection of gynecologic cancer cell types by conventional FDG-PET imaging. These findings demonstrate the feasibility of imaging endometrial and other gynecological cancers which have upregulated EMP2 expression using recombinant anti-EMP2 antibodies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5310. doi:10.1158/1538-7445.AM2011-5310