VALIDATION OF A KINETIC MODEL FOR RECEPTOR IMAGING

拟议的项目将继续调查放射性药物动力学。 受体特异性放射性示踪剂的建模。这一新的阶层 放射性药物，它凭借其在靶组织中的聚集 对特定受体分子的亲和力，为 体内受体生物化学的无创性研究。释义 有关受体化学信息的示踪数据将需要 一个动力学模型。我们已经测试了一个肝脏摄取的动力学模型 甘油三酯-99m半乳糖基-新糖白蛋白(TcNGA)在健康猪体内，发现 受体浓度和亲和力以及肝脏血液的模型估计 流量与实际值相一致，这些值是由 已有的技术。 我们将修改动力学模型以纳入以下条件： 1)受体循环，2)血清内源性激素浓度升高 配体，3)纤维蛋白生成，阻碍大分子的扩散 穿过肝硬变内的肝窦，以及4)区域性 流和受体功能的异质性。 在对模型进行适当修改后，上述内容将 调查方式如下：1)使用肝细胞灌注器 模拟有(37摄氏度)和无受体的细胞摄取的电路 回收(4摄氏度)。2)TcNGA期间血清内源性配体测定 领悟。3)研究不同标记配体对肝硬变犬的影响 分子量。4)研究了海流模型和轴向分布 使用从PET成像获得的区域动力学数据的模型 镓-68-去铁胺-NGA。模特候选人将接受有效性测试 (适合度、似是而非、可辨识性)。 对这些问题的回答将使我们能够开发一种模型，该模型将 适用于广泛的病理生理学。开发一种 正电子标记的NGA将使我们能够开发和验证 肝脏血流量和受体生化的区域测量。基座 根据我们过去的工作，我们知道TcNGA模型是可测试的，因此， 提供了一个广泛研究 健康和病变组织中的放射性药物动力学系统。因此，这一点 该项目将通过生理学推动功能成像技术的发展 模特儿。

The proposed project will continue to investigate the radiopharmacokinetic modeling of receptor-specific radiotracers. This new class of radiopharmaceutical, which accumulates at a target tissue by virtue of its affinity for a specific receptor molecule, offers an opportunity for the noninvasive study of in vivo receptor biochemistry. Interpretation of the tracer data into information concerning the receptor chemistry will require a kinetic model. We have tested a kinetic model for the hepatic uptake of Tc-99m galactosyl-neoglycoalbumin (TcNGA) in healthy pigs, and found the model estimates of receptor concentration and affinity, and hepatic blood flow to agree with the actual values which were measured independently by established techniques. We will modify the kinetic model to incorporate the following conditions: 1) receptor recycling, 2) elevated serum concentration of endogenous ligand, 3) fibrinogenesis, which impedes the diffusion of macromolecules across the hepatic sinusoids within cirrhotic livers, and 4) regional heterogeneity of flow and receptor function. After appropriate modifications to the model, the above will be investigated in the following manner: 1) Use a hepatocyte perifusion circuit to model cell uptake with (37 degrees C) and without receptor recycling (4 degrees C). 2) Assay serum for endogenous ligand during TcNGA uptake. 3) Study cirrhotic dogs with labeled ligands of differing molecular weights. 4) Study the current model and an axial distributed model using regional kinetic data obtained from PET imaging of Gallium-68-deferoxamine-NGA. Model candidates will be tested for validity (goodness-of-fit, plausibility, identifiability). Answers to these questions will permit us to develop a model that will be valid for a wide spectrum of pathophysiology. Development of a positron-labeled NGA will allow us to develop and validate a model for the regional measurement of liver blood flow and receptor biochemistry. Based on our past work we know that the TcNGA model is testable, and as a result, offers an opportunity to extensively study the behavior of a radiopharmacokinetic system in healthy and diseased tissue. Thus, this project will advance the technique of functional imaging via physiologic modeling.