PET VS GAMMA SCINTIGRAPHY FOR LUNG BIODISTRIBUTION STUDIES

此前，CWRU/克利夫兰大学医院与罗纳-普伦克·罗勒(RPR)合作并赞助的研究已经获得了有关曲安奈德(TAA)的生物分布和药代动力学的有用数据。TAA是两种已有的RPR药物(Nasacort和Azmacort)的活性成分。在过去的研究中，我们建立了生产碳-11标记TAA并将其用于PET研究的能力。研究表明，PET技术可以重复性地定量药物制剂中有效成分的生物分布。虽然用正电子发射计算机断层扫描进行剂量量化是准确的，但用正电子发射计算机断层扫描得到的结果与其他人以前用常规伽玛闪烁照相得到的结果有明显的差异。伽马相机只能显示药物的平面图，分辨率很低。分辨率是离相机表面距离的递减函数，其他人在研究中关于数据采集和数据处理的方法的数据是不可用的。因此，伽马相机和PET测量的表观剂量分布之间的差异可能是伽马成像所涉及的衰减、灵敏度和误差的伪影，也可能是由于药物配方的不同造成的。为了回答这个问题，有必要在相同的实验对象中进行PET和伽马闪烁成像的比较研究，以确定从给定的药物分布获得的结果之间的关系。本研究的目的是用正电子发射计算机断层扫描(PET)和伽玛闪烁照相技术定量评价TAA在肺内的生物分布，以便对这两种方法进行比较。将使用伽马闪烁成像数据采集的几种变体来查看每个标记的给药，以便进行多方法比较。血药动学测定将作为常规给药方法给药的量度。这项研究遵循开放标签、随机、交叉设计。PET扫描将以开发并成功用于先前[11C]曲安奈德(Azmacort)研究的相同方式进行。处方的放射性药物将在站立状态下按包装说明口服给药，然后在仰卧位进行PET数据采集。这项研究的人群将由24名健康的男性志愿者组成。符合条件的受试者将被要求向大学医院的核医学部报告。静脉导管将被放置在手臂上，用于采集血液进行常规药代动力学8小时。在给药后，他们将立即被放置在扫描场中，并接受长达两个小时的动态PET成像。受试者将被带到GCRC进行观察，完成药代动力学采样，并进行样品处理。

Previous studies which have been at CWRU/University Hospitals of Cleveland in collaboration with and sponsored by Rhone-Poulenc Rorer (RPR) have obtained useful data concerning the biodistribution and pharmacokinetics of triamcinolone acetonide (TAA). TAA is the active ingredient in the two established RPR drugs (Nasacort and Azmacort). In past studies our ability to produce carbon-11 labeled TAA and to use it in PET studies was established. The studies showed that the PET technique can be used to reproducibly quantify the biodistribution of the active ingredient of the drug preparations. Though the dose quantification by PET was accurate, there are appaent differences between the results obtained with PET and results previously obtained by others using conventional gamma scintigraphy. A gamma camera shows only a planar view of the drug with poor resolution. The resolution is a diminishing function of distance from the face of the camera, and other data concerning methods of data acquisition and data treatment in the studies by others are not available. The discrepancy between apparent dose distribution as measured by gamma camera and by PET may therefore be an artifact of the attenuation, sensitivity, and errors involved in gamma imaging, or they may be due to differences in drug formulation. In order to answer this question, it is necessary to perform a comparative study of PET and gamma scintigraphy in the same experimental subjects to determine the relationship between the results obtained from a given drug distribution. The objective of this study is to quantitatively evaluate the biodistribution of TAA in the lungs by PET and gamma scintigraphy so that the two methods may be compared. Several variations of gamma scintigraphy data acquisition will be used to view each labeled drug administration in order to allow a multi-method comparison. Plasma pharmacokinetics will be determined as a measure of the dose administration by conventional means. The study follows an open label, randomized, crossover design. PET scanning will be performed in the same fashion as was developed and successfully used for previous studies of [11C]triamcinolone acetonide (Azmacort). The formulated radiopharmaceutical will be administered orally according to package directions to normal volunteers while standing, followed by PET data acquisition in the supine position. The population of this study will consist of 24 healthy male volunteers. Qualifying subjects will be asked to report to the division of Nuclear Medicine at University Hospitals. A venous catheter will be placed in an arm, for sampling blood for conventional pharmacokinetics for 8 hours. Immediately after dosing, they will be positioned in the scan field and undergo dynamic PET imaging for up to two hours. The subject will be taken to the GCRC for observation, completion of pharmacokinetic sampling, and sample processing.