VALIDATION OF A KINETIC MODEL FOR RECEPTOR IMAGING

拟议项目将继续研究放射性药物动力学 受体特异性放射性示踪剂的建模。 这类新的 放射性药物，其凭借其在靶组织处积聚， 对特定受体分子的亲和力，提供了一个机会， 体内受体生物化学的非侵入性研究。 解释 将示踪剂数据转化为有关受体化学的信息将需要 动力学模型 我们已经测试了肝摄取的动力学模型， Tc-99 m半乳糖基-新糖蛋白（TcNGA）在健康猪中的作用，并发现 受体浓度和亲和力以及肝血的模型估计值 流量与独立测量的实际值一致， 建立技术。 我们将修改动力学模型，以纳入以下条件： 1)受体再循环，2）血清内源性受体浓度升高 配体，3）纤维蛋白生成，其阻碍大分子的扩散 穿过硬化肝脏内的肝窦，以及4）区域性 流动和受体功能的异质性。 在对模型进行适当修改后， 以下列方式研究：1）使用肝细胞灌流 电路，以模拟具有（37摄氏度）和不具有受体的细胞摄取 回收（4摄氏度）。 2)TcNGA期间内源性配体的测定血清 摄取。 3)研究用不同的标记配体标记的狗 分子量 4)研究了电流模型和轴向分布的 模型使用从PET成像获得的局部动力学数据， 镓-68-去铁胺-NGA 模范候选人将接受有效性测试 （拟合优度、可识别性、可识别性）。 这些问题的答案将使我们能够开发一个模型， 适用于广泛的病理生理学。 发展 正电子标记的NGA将使我们能够开发和验证一个模型， 肝血流量和受体生物化学的区域测量。 基于 在我们过去的工作中，我们知道TcNGA模型是可测试的，因此， 提供了一个机会，广泛研究的行为， 在健康和患病组织中的放射性药物动力学系统。 因此， 该项目将通过生理功能成像技术 建模

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.