PET VS GAMMA SCINTIGRAPHY FOR LUNG BIODISTRIBUTION STUDIES

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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.