Abstract B15: The use of micro-CT imaging and histology in a clinically relevant Foxn1nu mouse intrafemoral model of metastatic prostate cancer.

Abstract

Abstract Subcutaneous tumor xenograft models using transplantation of human tumour cell lines into immunodeficient mice are routinely used for the preclinical testing of anticancer therapies. These models do not however fully represent the clinical situation, and as such there can be difficulties in translating the results of promising preclinical data into a successful patient treatment. There is therefore a need to develop more clinically relevant preclinical models, particularly in metastatic disease. The development of preclinical imaging strategies, such as micro-CT gives us the ability to follow disease progression at orthotopic sites, and the efficacy of treatment longitudinally in a similar way to the clinical situation. At autopsy, approximately 84% of patients with prostate cancer will be found to have skeletal metastases, and in those patients who first present with bony disease the 5 year survival rate is less than 25%, making this an important focus for the development of novel therapies. Intrafemoral (i.f.) transplantation is a technically feasible and convenient method for the study of cancer types associated with bone or bone marrow, as this technique implants cells directly into the biological niche of interest, correlating with the environment in which disease develops in patients. Previously, severely compromised immunodeficient mice have been used to study metastatic prostate cancer development. For the studies described here, using the immunocompromised Foxn1nu mouse strain, the human prostate cancer cell lines PC3 (prostate membrane specific antigen negative, androgen resistant) or LNCaP (prostate membrane specific antigen positive, androgen sensitive) were injected i.f. into the bone marrow cavity of the femur via the knee joint. Animals were followed over a period of several weeks, and micro-CT imaging used to assess the growth and development of tumour in bone. Areas of interest, identified by imaging, were taken for histological assessment of patient relevant markers, and data compared to clinical imaging and histopathology of human disease. We have found that this model offers a clinically relevant preclinical representation of bony metastasis of prostate cancer. The described use of micro-CT imaging and detailed histological analysis allows for a clearer translation between preclinical testing and clinical observation, and as such represents a valuable new tool for the assessment of novel therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B15.