In vitro binding profile and radiosynthesis of a novel 18F-labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter


In vitro binding profile and radiosynthesis of a novel 18F-labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter

Wenzel, B.; Hiller, A.; Fischer, S.; Sorger, D.; Deuther-Conrad, W.; Scheunemann, M.; Brust, P.; Sabri, O.; Steinbach, J.

Radiolabeled vesamicol analogues are promising candidates as ligands for the vesicular acetylcholine transporter (VAChT) to enable in vivo imaging of early cholinergic degenerations in brain. The 4-fluorobenzoyl substituted azaspirovesamicol derivative FBASV is one out of six novel vesamicol analogs and demonstrated most appropriate in vitro binding data. 18F-radiolabeling was performed by microwave assisted nucleophilic aromatic substitution of the corresponding nitro precursor and two methods were developed for the purification of [18F]FBASV. Utilizing method A, the remaining nitro precursor was reduced to its corresponding amine, which was separated via semi-preparative HPLC on a conventional RP column. In method B a phenyl column was used for the direct separation of [18F]FBASV and its nitro precursor, resulting in a change of the elution order and better separation parameters. Thus, [18F]FBASV was synthesized with a RCY of 16-18%, a specific activity > 300 GBq/µmol, and a radiochemical purity of > 99.5% suitable for future in vivo studies.

Keywords: azaspirovesamicol; [18F]FBASV; VAChT; PET; 18F-labeling; vesamicol; nitro precursor

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Publ.-Id: 15186