Molecular, functional and micro-morphological imaging of bone metastases in vivo

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The complexity of the bone microenvironment and the multitude of cell types interacting with each other during skeletal metastasis necessitate the development of technologies suited for multimodal molecular, functional and micro-morphological imaging of these processes in vivo. We will test the hypothesis whether molecular markers specific for osteoblasts, osteoclasts and tumor cell interaction can be employed to allow for longitudinal monitoring of these cells during skeletal metastasis at the microstructural level. An optical reporter gene placed under the control of the osteoblast tissue-specific promoter, α1(I)-collagen, will allow to label cells of the osteoblastic lineage in an immunodeficient mouse strain. Imaging methods based on fluorescent markers reflecting osteoblast induced matrix apposition, osteoclast number (αvβ3 integrin) and function (cathepsin K expression) will be developed to study tumor-bone interaction, e.g. with regard to Dickkopf-1. Multi-modality imaging combining fluorescent molecular tomography (FMT) and micro-computed tomography (micro-CT) will be optimized for quantitative longitudinal evaluation. Our work will result in validation of a robust basic armamentarium of quantifiable FMT/micro-CT markers and methods with potential to image tumor-bone interaction-specific targets which are characterized in partner projects. Such methods will augment the ability to non-invasively monitor metastatic processes also in response to treatment.