Core--In vivo imaging

（申请人描述）体内成像核心将通过提供一种独特的、无创的评估来支持SPORE的所有3个项目(1)在卵巢癌生长和扩散中重要的受体，（2)通过腺病毒载体靶向肿瘤，以及(3)结合治疗评估的细胞凋亡途径）。此外，核心将进行器官功能的研究。核心的基础设施已经存在，是通过内部机制通过竞争性筹资建立的。在过去两年中已经开发的放射性示踪剂将用于拟议的成像评价。大多数成像实验将在动物模型中进行。然而，预计随着报告系统在动物模型中成像基因转移的验证，这种能力将被转化为I期临床测试。核心将支持第一阶段测试的这一部分，这将是可能的，因为放射性药物是一种批准的人类药物。Core提供的成像数据将与其他模式（如免疫组织学）互补，以评估卵巢癌。成像的优点包括它是可重复的，非侵入性的，并且能够随着时间的推移评估整个动物模型（或人类）。核心有两个专用的伽玛相机用于动物实验，与相邻的动物住房设施（隔离器）。这些设备和设施，加上放射化学方面的专业知识，几乎可以用Tc-99m对任何蛋白质分子进行放射性标记，并用于动物模型的成像。Tc-99m的优点包括半衰期短（6小时）、低成本、持续可用性，以及由于其丰富的低能量伽马射线发射而易于成像。迄今为止，超过25种不同的蛋白质分子已经被Core的科学家用Tc-99m进行了放射性标记，包括短肽（例如针对e -选择素或生长抑素受体）、生长因子（FGF-1）、抗体和可溶性受体。在进行动物实验之前，这些放射性标记蛋白要经过严格的体外评估。结合常数由Scatchard分析确定，以确保对体内成像数据的正确解释。

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.