ABSTRACT: [F-18]Mefway was developed to provide an F-18 labeled PET neuroligand with high affinity for the serotonin 5-HT(1A) receptor to improve the in vivo assessment of the 5-HT(1A) system. The goal of this work was to compare the in vivo kinetics of [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 in the rhesus monkey.METHODS:: Each of four monkeys were given bolus injections of [F-18]mefway, [C-11]WAY100635, and [F-18]MPPF and scans were acquired with a microPET P4 scanner. Arterial blood was sampled to assay parent compound throughout the time course of the PET experiment. Time activity curves were extracted in the high 5-HT(1A) binding areas of the anterior cingulate cortex (ACG), mesial temporal cortex (MTC), raphe nuclei (RN) and insula cortex (IC). Time activity curves were also extracted in the cerebellum (CB) which was used as a reference region. The in vivo kinetics of the radiotracers were compared based upon the nondisplaceable distribution volume (V(ND)) and binding potential (BP(ND)). RESULTS:: At 30 minutes, the fraction of radioactivity in the plasma due to parent compound was 19%, 28%, and 29% and cleared from the arterial plasma at rates of 0.0031, 0.0078, and 0.0069 (min-1) ([F-18]mefway, [F-18]MPPF, [C-11]WAY100635). The BP(ND) in the brain regions were; MTC: 7.4±0.6, 3.1±0.4, 7.0±1.2, ACG: 7.2±1.2, 2.1±0.2, 7.9±1.2; RN: 3.7±0.6, 1.3±0.3, 3.3±0.7 and IC: 4.2±0.6, 1.2±0.1, 4.7±1.0 for [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 respectively. CONCLUSIONS:: In the rhesus monkey, [F-18]mefway has similar in vivo kinetics to [C-11]WAY100635 and yields greater than 2-fold higher BP(ND) than [F-18]MPPF. These properties make [F-18]mefway a promising radiotracer for 5-HT(1A) assay, providing higher counting statistics and a greater dynamic range in BP(ND). Proteins 2010. © 2010 Wiley-Liss, Inc.
Synapse 10/2010; · 2.94 Impact Factor