Synthesis and biological evaluation of [18F]C for in vivo studies of dopamine D4 receptor

AIM: The 7-azaindole derivative(L-750, 667) is a novel, high-affinity (Ki = 0.43 nmol · L-1) and selective dopamine D4 R ligand. We synthesized and evaluated 3-{[-4-(4-[18F] fluorophenyl) methyl]piperazin-1-yl}-methyl-1H-pyrrolo [2,3-b] pyridine([18F] C), which is an analog of L-745, 870 binding D4 receptor in vitro. METHODS: The [18F]C was prepared by reductive alkylation of 3-(piperazin-1-yl)-methyl-1H-pyrrolo [2, 3-b] pyridine with 4-[18F] fluorobenzaldehyde in radiochemical yield (decay-corrected, 9.0% ∼ 12.0%) and with high specific activity (>37 GBq · μmol-1). RESULTS: A higher uptake w0as observed in the frontal cortex and hippocampus (0.43 % ID/g, 0.35% KID/g) compared to the striatum, The radioactivity in the medulla displayed higher uptakes than into others regional at all time points. CONCLUSION: Tissue distribution studies in rats demonstrated specific distribution of the [18 F]C in brain regions, suggesting that this radioligand may be a suitalble agent for in vivo studies of dopamine D4 receptor.