VALIDATION OF A KINETIC MODEL FOR RECEPTOR IMAGING

该建议的具体目的是验证动力学模型， 分析了一种新的核医学模式的结果。 这种技术 使用肝细胞特异性受体结合放射性药物， Tc-99 m-半乳糖基-新糖蛋白（Tc-NGA）。 Tc-NGA的动力学分析 时间-活动数据产生模型参数的估计， 肝血流量、受体浓度、前向速率常数 受体结合、肝血和肝外血容量以及Tc-NGA 新陈代谢. 本项目将使用以下方法测量上述参数 建立技术。 这些测量将在Tc-NGA期间进行 犬肝脏功能成像。 这些技术将包括： i）使用吲哚菁绿色提取物测定肝血流量 用肝静脉取样测量; ii）测量 受体，和使用体外结合的正向速率常数 测定;和iii）肝和肝外血容量的测量 使用铬标记的红细胞和碘化白蛋白。 比较 通过Tc-NGA功能成像研究估计的每个值和实际值 将在不同的肝血流量、肝脏质量和 前向结合速率常数。 这将通过以下方式实现：a）成像 不同体重的狗，B）用以下药物控制肝血流： 不同水平的氟烷麻醉或胰高血糖素静脉注射;以及 c）注射不同碳水化合物密度的NGA。 如果动能 模型是受体对Tc-NGA摄取的有效表示， HPB量、肝血流量和血流量的参数估计 体积将与整个肝脏范围内的测量值一致 血流量、肝质量和前向结合速率常数。 Tc-NGA功能成像的当前临床应用使用 作为肝功能指标的参数估计值。 验证 动力学模型将提供生理化学基础， 可以解释。 这种技术可以用于研究体内 特定受体的生物化学，以及疾病的影响 和药理学试剂对肝血流的影响。

The specific aim of this proposal is to validate a kinetic model which analyzes the results of a new nuclear medicine modality. This technique employs a hepatocyte-specific receptor-binding radiopharmaceutical, Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA). Kinetic analysis of Tc-NGA time-activity data yields estimates of model parameters which represent hepatic blood flow, receptor concentration, the forward rate constant of receptor biding, hepatic blood and extra-hepatic blood volumes, and Tc-NGA metabolism. This project will measure each of the above mentioned parameters using established techniques. These measurements will be made during Tc-NGA functional imaging of canine livers. The techniques will include: i)\determination of hepatic blood flow using indocyanine green extraction measurements with hepatic venous sampling; ii) measurement of the number of receptors, and the forward rate constant of binding using an in vitro assay; and iii) measurement of hepatic and extra-hepatic blood volumes using chromium-labeled red blood cells and iodinated albumin. Comparison of each value estimated by the Tc-NGA function imaging study and the actual value will be carried out at different hepatic blood flows, liver mass, and forward binding rate constants. This will be accomplished by: a) imaging dogs of differing bodyweight, b) controlling hepatic blood flow with varying levels of halothane anesthesia or i.v. injections of glucagon; and c) injecting NGAs of differing carbohydrate densities. If the kinetic model is a valid representation of Tc-NGA uptake by the receptor, the parameter estimates of the amount of HPB, hepatic blood flow, and blood volumes will agree with the measured values throughout the range of liver blood flows, hepatic mass, and forward binding rate constants. Current clinical application of Tc-NGA functional imaging uses the parameter estimates as indexes of hepatic function. Validation of the kinetic model will provide a physiochemical basis upon which each parameter may be interpreted. This technique could then be used to study the in vivo biochemistry of the specific receptor, as well as, the influence of disease and pharmacologic agents upon hepatic blood flow.