BLOOD POOL CONTRAST AGENTS FOR CT AND MRI

CT 和 MRI 血池造影剂

• 批准号: 6633455
• 负责人: David R. Vera
• 金额: $ 31.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633455
• 关键词: bioimaging /biomedical imaging; blood drug; cardiovascular imaging /visualization; computed axial tomography; contrast media; dextrans; diethylenetriaminepentaacetate; drug design /synthesis /production; gadolinium; magnetic resonance imaging; neoplasm /cancer blood supply

DESCRIPTION (Adapted from Applicant's Abstract): The investigators propose a project in which they will synthesize and test a new class of blood pool agents for computed tomography (CT) and magnetic resonance (MR) imaging. The proposal includes preliminary data demonstrating that the proposed agent enhanced CT visualization of hepatic vessels and provided MR detection of tumor vasculature for an extended period of time. The proposed agent is based on a molecular backbone of dextran to which multiple reporter units of Gd-DTPA are covalently attached. Using dextran as a molecular backbone offers many advantages. First, the fact that the agent is not a particle should increase biological safety. Second, dextran is available in a variety of molecular weights; this will make it possible to optimize the agent's blood residence time and tumor permeability. Third, dextran is composed of repeating glucose units, each of which has three potential attachment sites fore each Gd-DOTA-reporter unit. This property will permit optimization of the agent. Fourth, the extensive human use experience with dextran increases the probability that the agent will be safe. The objective is to develop a new class of imaging agent with the appropriate attributes for detection of tumors and other tissue pathology resulting from abnormal tissue vascularity. These attributes include adequate blood enhancement, favorable residence time within the blood, chemical stability in vitro and in vivo, and high plasma specificity. The project has five specific aims. 1) The first is a level of enhancement that will give hepatic vessels a twofold greater signal than hepatic tissue. After preliminary CT and MR imaging studies in rabbits during the Years-01 and B02, a crossover design will be used to compare the CT and MR imaging properties of the new, optimized agent with those of standard contrast media. 2) Plasma half-time of one hour will be achieved by selection of dextran size and reporter density. Preliminary data indicate that a dextran backbone will a molecular weight of 10 g/mole and a reporter density of two Gd-DOTA units per glucose should accomplish this goal. Plasma clearance will be measured using Gd-153- and C-14-labeled agents. 3) To verify the stability of the Gd-complex; the investigators will test in vitro stability and dissociation inertia. 4) The investigators will measure the agent's biodistribution using radiolabeled components (Gd-153, C-14-DOTA, C-14-methyl-dextran, and a S-35 label for the Dota-to-dextran leash). 5. During the 4-year project the investigators will scale-up the synthesis and maximize reporter densities. At the completion of this project, the necessary information will be available to determine the clinical potential as a new blood pool agent for CT and MR imaging. This agent is expected to provide increased sensitivity for cancer detection and staging, greater imaging flexibility, and increased patient comfort. Additionally, this structure will serve as a neural carrier of for future class of nonparticulate receptor-binding CT and MR contrast media.

描述（根据申请人的摘要改编）：调查人员提出了 他们将合成并测试新的血池代理的项目 用于计算机断层扫描（CT）和磁共振（MR）成像。 提案 包括初步数据，表明提出的代理增强了CT 肝血管的可视化并提供了肿瘤脉管系统的MR检测 长时间。 所提出的剂基于分子 Dextran的骨干，GD-DTPA的多个记者单位共价为 随附的。 使用葡萄糖作为分子骨架具有许多优势。 首先，代理不是粒子应该增加生物学的事实 安全。 其次，葡聚糖有多种分子量。这 将有可能优化特工的血液停留时间和肿瘤 渗透性。 第三，葡聚糖由重复的葡萄糖单位组成 每个GD-Dota-Reporter单元都有三个潜在的附件位点。 该属性将允许对代理进行优化。 第四，广泛 葡萄兰的人使用经验增加了代理商的可能性 安全。 目的是用 检测肿瘤和其他组织病理学的适当属性 由异常组织血管产生。 这些属性包括足够的 血液增强，血液中有利的停留时间，化学 体外和体内的稳定性以及高血浆特异性。 该项目有 五个具体目标。 1）第一个是增强水平 肝血管比肝组织大两个。 后 在01年和B02期间，兔子的初步CT和MR成像研究，A 跨界设计将用于比较CT和MR成像特性 新的，优化的代理具有标准对比介质。 2）血浆 通过选择葡聚糖尺寸和 记者密度。 初步数据表明，葡聚糖骨架将a 分子量为10 g/摩尔的分子量和一个2个GD-DOTA单元的记者密度 葡萄糖应实现这一目标。 血浆清除将使用 GD-153-和C-14标记的剂。 3）验证GD复合物的稳定性； 研究人员将测试体外稳定性和解离惯性。 4） 调查人员将使用放射性标记测量代理的生物分布 组件（GD-153，C-14-DOTA，C-14-甲基 - 脱骨和S-35标签 dota-to-dextran皮带）。 5。在4年项目中，调查人员将 扩展合成并最大化报告基因密度。 完成 该项目，必要的信息将可用来确定 作为CT和MR成像的新血池药物的临床潜力。 这个代理 预计将对癌症检测和分期提高灵敏度， 更大的成像灵活性，并提高患者舒适性。 另外，这个 结构将作为未来非特定类别的神经载体 受体结合CT和MR对比介质。