CARBON-11-FLB-457 - A RADIOLIGAND FOR EXTRASTRIATAL D2 DOPAMINE-RECEPTORS

D2 dopamine receptors in extrastriatal brain regions are of central in terest for research in schizophrenia and antipsychotic drugs. This art icle reports the development of [C-11]FLB 457 for PET examination of e xtrastriatal D2 dopamine receptors. Methods: Carbon-11-FLB 457 was pre pared by O-methylation of FLB 604 (2-hydroxy precursor) with [C-11]met hyl iodide. Total radiochemical yield was 25%-35% within a total synth esis time of 30 min. The specific radioactivity at the end of synthesi s was about 1300 Ci/mmole (48 GBq/mu mole). Results: FLB 457 bound wit h high affinity to D2 and D3 dopamine receptors, whereas binding to ot her putative central receptors was negligible. PET studies in Cynomolg us monkeys demonstrated 15 times higher accumulation of radioactivity in the striatum than in the cerebellum after 60 min. Uptake in the tha lamus and neocortex, extrastriatal regions with a low density of D2 do pamine receptors, was, respectively, 4 and 2.5 times higher than in th e cerebellum. Radioactivity was displaced by raclopride and haloperido l which confirms the selectivity and reversibility of [C-11]FLB 457 bi nding to D2 dopamine receptors in vivo in the striatum, thalamus and n eocortex. Conclusion: Carbon-11-FLB 457 should be a useful PET ligand for quantitative examination of D2 dopamine receptors in extrastriatal regions in the human brain.