Abstract
906
Objectives: The histamine H3 receptor is implicated in the pathophysiology of several CNS disorders. GSK189254 is a highly potent, selective and brain penetrant H3 receptor antagonist. Previous studies in the pig have shown that [11C]GSK189254 uptake in H3 rich regions of the brain can be blocked by the selective H3 antagonist, ciproxifan (1). The aim of this study was to evaluate [11C]GSK189254 in man.
Methods: The regional brain distribution of [11C]GSK189254 was investigated in 14 healthy subjects (35-49y). Each subject was scanned following i.v. administration of ca. 10mCi of [11C]GSK189254 pre and post a single oral dose of GSK189254 (10-100µg).
Results: [11C]GSK189254 readily entered the brain; its regional brain distribution reflected the known distribution of H3 receptors, with high binding in the caudate and putamen, intermediate binding in cortical regions and lower levels in the cerebellum. Pretreatment with oral GSK189254 reduced the uptake of [11C]GSK189254, e.g. following a 50µg dose, VT decreased from 74±27 and 28±4 (n=13) to 16±3 and 12±1 (n=3)(mean±SD) in the caudate and frontal cortex, respectively. Estimates of VND were obtained by graphical analysis (10±1, mean±SD).
Conclusions: [11C]GSK189254 can be used to quantify H3 receptor availability in humans in vivo using PET.
- Society of Nuclear Medicine, Inc.