Convergent 18 F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT 2A receptor PET ligands.

Positron emission tomography (PET) investigations of the 5-HT2A receptor (5-HT2A R) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a11 C-labeled agonist PET ligand ([11 C]Cimbi-36), and the aim of this study was to identify a18 F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different18 F-labeled ligands structurally related to Cimbi-36 from a common18 F-labeled intermediate. After intravenous injection, all ligands entered the pig brain. However, since within-scan intervention with ketanserin, a known orthosteric 5-HT2A receptor antagonist, did not result in significant blocking, the radioligands seem unsuitable for neuroimaging of the 5-HT2A R in vivo.