Radiosynthesis of 3-{ [4- (4-[18F]fluorobenzyl)]piperazin-1-yl)methyl-1H-pyrrolo[2,3-b]pyridine: A potential dopamine D4 receptor imaging agent

The dopamine D 4 receptor (D 4 R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but to date no selective positron emission tomography (PET) ligand is available to study its distribution in vivo. The 7-azaindole derivative 3- { [4-(4-iodophenyl)piperazin- 1-yl]-methyl}- I H-pyrrolo [2,3-b]pyridine (L-750,667) is a novel, high-affinity (K i = 0.51 nM) and selective D 4 R ligand. L-750,667 analogue 3-{[4-(4-[ 1 8 F]fluorobenzyl)]piperazin-l-yl}methyl-1H-pyrrolo[2,3-b]-pyridine was prepared by reacting 3-(piperazin-l-yl)-methyl-1H-pyrrolo[2,3-b]pyridine with 4-[ 1 8 F]fluorobenzaldehyde, which was labeled with no carrier added [ 1 8 F]fluoride. The radiochemical yield of 3-{ [4-(4-[ 1 8 F]fluorobenzyl)]piperazin-1-yl}methyl-1 H-pyrrolo[2,3-b]pyridine was 12.0% at end of synthesis (EOS), and the synthesis time was 73 min. The labeled benzaldehydes may be useful precursors for the radiosyntheses of other complex radiotracers for PET.