title: Brain uptake of the acid metabolites of F-18-labeled WAY 100635 analogs.
abstract: The 5-HT1A ligands [ 18F]FPWAY and [ 18F]FCWAY are metabolized to [ 18F]fluorobenzoic acid (FB) and [ 18F]fluorocyclohexanecarboxylic acid (FC), respectively. To quantify the penetration of these acids into the brain, dynamic positron emission tomography studies were performed in rhesus monkeys with [ 18F]FB and [ 18F]FC. High-performance liquid chromatography analysis of arterial blood samples showed no metabolites for [ 18F]FB, whereas [ 18F]FC was rapidly metabolized to [ 18F]fluoride. A model with one tissue compartment and vascular radioactivity was used to analyze gray matter time-activity curves. For [ 18F]FC, an additional term was added to account for [ 18F]fluoride skull spillover into the brain; this term accounted for 70% to 90% of the measured radioactivity concentration at 90 minutes. For [ 18F]FB, mean gray matter parameters were as follows: K1, 10 +/- 3 micro L. min(-1). mL(-1); distribution volume, 0.052 +/- 0.006 (mL/mL). For [ 18F]FC, the values were as follows: K1, 15 +/- 4 micro L. min(-1). mL(-1); V, 0.29 +/- 0.06 mL/mL. The values were consistent with a physiologic model that included brain-to-blood pH difference and the plasma free fraction of the acid. Simulations based on [ 18F]FCWAY human data showed that [ 18F]FC uptake produces significant biases in estimates in regions with low specific binding. These results can be used to correct the tissue [ 18F]FCWAY time-activity data for brain uptake of [ 18F]FC using the measured [ 18F]FC input function.
authors.affiliation: Positrom Emission Tomography Department, W.G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. richard-e-carson@nih.gov
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wu
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Der
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D000818:Animals; D001565:Benzoates / Q000493:pharmacokinetics*; D001769:Blood / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D003509:Cyclohexanecarboxylic Acids / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D008959:Models, Neurological; D010487:Periaqueductal Gray / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D001565:Benzoates; D003509:Cyclohexanecarboxylic Acids; D005462:Fluorine Radioisotopes; D008024:Ligands; C022893:4-fluorobenzoic acid