An improved synthesis of [18F]VAT and its precursor

The synthesis method for a clinical interesting18F-labeled radiotracer, [18F]VAT, has been improved by regio- and enantio-enriched synthesis of intermediate benzovesamicol (-)5 and tosylate (-)8 as radiolabeling precursors. The simplifed radiosynthesis process features with one-step radiolabeling and much shortened production time. The vesicular acetylcholine transporter (VAChT) in the brain is an important presynaptic cholinergic biomarker, and neuroimaging studies of VAChT may provide in vivo information about psychiatric and neurologic conditions including Alzheimer's disease that are not accessible by other methods. The18F-labeled radiotracer, ((-)-(1-(-8-(2-[18F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([18F]VAT,1), was reported as a selective and high affinity ligand for the in vivo imaging of VAChT. The synthesis of [18F]VAT has been reported in a two-step procedure with total 140  min, which includes preparation of 2-[18F]fluoroethyltosylate and alkylation of benzovesamicol(-)-5 precursor with this radiosynthon using two different automated production modules consecutively. A multiple step synthetic route was employed for the synthesis of stereospecific precursor benzovesamicol(-)-5, which is difficult to be adapted for scale-up. To make the production of this tracer more amenable for clinical imaging, we present an improved total synthesis protocol to attain [18F]VAT: (1) a tosylethoxy group being pre-insta...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research