Core--In vivo imaging

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DESCRIPTION: (Applicant's Description) The In Vivo Imaging Core will support all 3 programs in the SPORE by providing a unique, non- invasive evaluation of (1) receptors important in the growth and spread of ovarian cancer, (2) tumor targeting via adenoviral vectors, and (3) apoptosis pathways in conjunction with therapy evaluation. In addition, the Core will conduct studies of organ function. The infrastructure for the core already exists, having been established by competitive funding through an internal mechanism. Radiotracers already developed over the past two years will be utilized for the proposed imaging evaluations. The majority of the imaging experiments will be conducted in animal models. However, it is anticipated that following validation of the reporter system for imaging gene transfer in the animal model, this capability will be translated to the phase I clinical testing. The Core will support this part of the phase I testing, which will be possible since the radiopharmaceutical is an approved human agent. Imaging data provided by the Core will be complementary to other modes, such as immunohistology, to evaluate ovarian cancer. The advantages of imaging include the fact it is repeatable, non-invasive, and capable of evaluating the entire animal model (or human) over time. The Core has two dedicated gamma cameras for animal experimentation, with adjacent animal housing facilities (Isolators). These equipment and facilities, coupled with the expertise in radiochemistry, allow virtually any protein molecule to be radiolabeled with Tc-99m and used for imaging in animal models. The advantages to Tc-99m include its short half-life (6 hours), low cost, constant availability, and ease in imaging due to its abundant, low energy gamma-ray emission. To date, over 25 different protein molecules have been radiolabeled with Tc-99m by the Core's scientists, including short peptides (e.g. for targeting E-selectin or somatostatin receptors), growth factors (FGF-1), antibodies, and soluble receptors. These radiolabeled proteins are subjected to stringent in vitro evaluations prior to conducting animal experimenta tion. Binding constants are determined by Scatchard analyses to insure correct interpretation of the in vivo imaging data.