Core--In vivo imaging

核心--活体成像

• 批准号: 6228606
• 负责人: Kurt R Zinn
• 金额: $ 2.07万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6228606
• 关键词: Adenoviridae; apoptosis; bioimaging /biomedical imaging; biomedical facility; ovary neoplasms; radiotracer; receptor; transfection /expression vector

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.

描述：（申请人的描述）体内成像核心将通过对（1）对（1）对卵巢癌的生长和传播重要的受体进行独特的，非侵入性的评估来支持孢子中的所有3个程序，（2）通过腺病毒载体靶向肿瘤，以及（3）与治疗评估一致的凋亡途径。 此外，核心将进行器官功能研究。 核心的基础设施已经存在，已经通过内部机制建立了竞争性资金。 过去两年中已经开发的放射性示例将用于拟议的成像评估。 大多数成像实验将在动物模型中进行。 但是，可以预料，在对动物模型中对基因转移的成像转移的验证后，该能力将转化为I期临床测试。 核心将支持I阶段测试的这一部分，这将是可能的，因为放射性药物是批准的人类药物。 核心提供的成像数据将与其他模式（例如免疫组织学）互补，以评估卵巢癌。 成像的优点包括它是可重复的，无创的，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马摄像机用于动物实验，并具有相邻的动物住房设施（隔离器）。 这些设备和设施，再加上放射化学的专业知识，几乎可以用TC-99M进行放射性标记，并用于动物模型中的成像。 TC-99M的优势包括其短期寿命（6小时），低成本，持续的可用性以及由于其丰富的低能伽马射线排放而导致的成像易于成像。 迄今为止，核心的科学家将超过25种不同的蛋白质分子与TC-99M进行了放射标记，包括短肽（例如，用于靶向E-选择蛋白或生长抑素受体），生长因子（FGFF-1），抗体和可溶性受体。 在进行动物实验之前，这些放射性标记的蛋白在体外评估中进行了严格的评估。 通过SCATCHARD分析确定结合常数，以确保对体内成像数据的正确解释。