Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor

Abstract In the search for a novel serotonin 7 (5-HT 7 ) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro . Among the studied compounds, ( R )-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol (( R )- 16 ), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [ 11 C]( R )- 16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT 7 receptor selective antagonist SB-269970 ( 1 ) resulted in limited decrease in the binding of [ 11 C]( R )- 16 , suggesting that this radioligand is not optimal for imaging the brain 5-HT 7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT 7 receptor PET radioligands.