Towards the development of new subtype-specific muscarinic receptor radiopharmaceuticals - Radiosynthesis and ex vivo biodistribution of [18F]3-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine

Muscarinic receptors have been implicated in neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia. Nineteen derivatives of thiadiazolyltetrahydropyridine (TZTP), a core that has previously shown high affinities towards muscarinic receptor subtypes, were synthesized and evaluated via in vitro binding assays. The title compound, a fluoro-polyethyleneglycol analog of TZTP (4c), was subsequently labelled with fluorine-18. Fluorine-18-labelled 4c was produced, via an automated synthesis, in an average radiochemical yield of 36% (uncorrected for decay), with high radiochemical purity (>99%) and high specific activity (326 GBq/mu mol; end-of-bombardment), within 40 min (n = 3). Ex vivo biodistribution studies following tail-vein injection of [F-18]4c in conscious rats displayed sufficient brain uptake (0.4%-0.7% injected dose / gram of wet tissue in all brain regions at 5 min post injection); however, there were substantial polar metabolites present in the brain, thereby precluding future use of [F-18]4c for imaging in the central nervous system.