Radiosynthesis and in vitro evaluation of the 5HT2 receptor ligand [N-11C-methyl]-1-[2,5-dimethoxy-4-iodophenyl]-2-methylaminopropane for PET

In vivo labelling of serotonergic receptors (5HT) could be a useful tool for understanding the physiological and pathophysiological role of neurodegenerative disorders. 1-[2,5-Dimethoxy-4-iodophenyl]-2-aminopropane (DOI), a well known agonist with high affinity to 5HT2 receptors, was labelled with C-11 for PET. Here we report the evaluation of the mono-methylated and dimethylated analogs of DOI for PET. The syntheses of [N-11C-methyl]-DOI ([11C]MDOI) and [N-11C-dimethyl]-DOI ([11C]DMDOI) were optimized resulting in radiochemical yields of up to 43%, allowing efficient production for clinical use. High affinities for the 5HT2A and 5HT2C receptors with a slight preference for 5HT2A were found for MDOI, similar to the highly potent hallucinogen DOI.