In vitro and in vivo evaluation of [18F]FHTP as a potential dopamine D4 receptor PET imaging agent

3-(4-[ 18 F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4- c ]pyridin-5-one ([ 18 F]FHTP) was in vitro and in vivo evaluated as a putative dopamine D 4 receptor radioligand. Its inhibition constant ( K i ) for cloned human dopamine D 4.2 receptor was determined to be 2.9 nM and it displayed a 2000-fold D 4 -selectivity over the D 2long subtype. Its partition coefficient (log P ) was measured to be 1.11. Biodistribution, blocking distribution and metabolism studies in rats demonstrated that the specific distribution of [ 18 F]FHTP in brain regions, suggesting that [ 18 F]FHTP may be a suitable PET imaging agent for in vivo studies of the dopamine D 4 receptor.