Abstract 2450: Optimization of spontaneous metastasis incidence and quantification in human tumor xenograft models using bioluminescence imaging

Abstract Introduction: Spontaneous metastasis models are sought after in order to assess the potential of therapies aimed at prevention or treatment of primary tumor metastases. While some human tumor xenograft mouse models show spontaneous metastasis, few show high tissue specific incidence. Commonly the growth of the inherently more advanced primary tumor also limits the ability to characterize far less advanced metastases. Bioluminescence imaging provides a quantitative and convenient means for assessing location, incidence and progression of metastases using metastatic luciferase expressing tumor lines. However, substantially greater light signal from the primary tumor inhibits the ability to find and track much smaller metastasis signals. Several approaches to optimizing metastasis incidence and quantification, and controlling primary tumor growth were used and compared in a MDA-MB-231-luc-D3H2LN xenograft model. Methods: To assess both mouse strain dependence and implant site dependence of primary tumor metastasis, MDA-MB-231-luc-D3H2LN cells (2x106) were implanted in either the mammary fat pad, the sacral region or the quadriceps in several mouse strains, including outbred nu/nu, SHO and nd/bg/xid. To control primary tumor growth in order to facilitate metastasis quantification, both surgical excision and radiation based growth inhibition of of the primary tumors were used. In all cases, whole body bioluminescence imaging was used to quantify metastasis incidence and growth. Shileding of the primary tumor was used in order to characterize smaller metastases. Results and Discussion: While the MDA-MB-231-luc-D3H2LN mammary fat pad implant model has been shown the metastasize spontaneously, tissue specific incidence is generally < 100% and the ability to quantify metastases severely limited by the substantially greater light signal overwhelming much smaller metastasis signals, even when primary tumor shielding is used. In this study, both surgical excision and radiation based primary tumor growth inhibition enhanced the ability to detect metastases in a variety of tissues, including lymph nodes and lungs. The mammary fat pad implant site and the SCID Beige strain provided the highest spontaneous metastasis incidence. Future work will test radiation timing and dose to further optimize metastasis quantification in this and other spontaneous metastasis models. 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 2450. doi:1538-7445.AM2012-2450