title: Syntheses of mGluR5 PET radioligands through the radiofluorination of diaryliodonium tosylates.
abstract: 3-Fluoro-1-((thiazol-4-yl)ethynyl)benzenes constitute an important class of high-affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of which have been labeled with fluorine-18 (t(1/2) = 109.7 min), to provide radioligands for molecular imaging of brain mGluR5 in living animal and human subjects with positron emission tomography (PET). Labeling in the 3-fluoro position of such ligands can be achieved through aromatic nucleophilic substitution of a halide leaving group with [(18)F]fluoride ion when a weakly activating m-nitrile group is present, but is generally very low yielding (<8%). Here we used a microfluidic reaction platform to show that greatly enhanced (up to 6-fold) radiochemical yields can be achieved from suitably synthesized diaryliodonium tosylate precursors. The presence of a m-nitrile or other activating group is not required. Similar conditions were adopted in a more conventional automated radiochemistry platform having a single-pot reactor, to produce mGluR5 radioligands with useful radioactivities for PET imaging.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Rm. B3 C346A, 10 Center Drive, Bethesda, MD 20892-1003, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Telu
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Chun
authors.forename: Fabrice G
authors.initials: FG
authors.lastname: Siméon
authors.forename: Shuiyu
authors.initials: S
authors.lastname: Lu
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D046210:Microfluidic Analytical Techniques; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D005462:Fluorine Radioisotopes; C578935:GRM5 protein, human; D008024:Ligands; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles