Preparation of [Br-76]FLB 457 and [Br-76]FLB 463 for examination of striatal and extrastriatal dopamine D-2 receptors with PET

Both FLB 457 and FLB 463, two substituted benzamides with high affinity for the dopamine D-2 receptors, were labeled with bromine-76 for PET investigations. [Br-76]FLB 457 was prepared by electrophilic substitution of the tributyltin precursor. The radiochemical yield was 80%. [Br-76]FLB 463 was prepared by a direct electrophilic substitution enhanced by the hydroxyl group of the debromo analogue, with a total radiochemical yield of 50%. Radiochemical and chemical purity values of the radioligands as analyzed by radio-TLC and HPLC were >99%, and the specific radioactivity was similar to 40 GBq/mu mol. During PET examinations of [Br-76]FLB 457 and [Br-76]FLB 463 binding in baboons there was a rapid and high uptake in the striatum. The striatal radioactivity concentration reached a plateau 1 h postinjection (p.i.). The striatum-to- cerebellum radioactivity concentration ratio increased from 11 at 1 h p.i., to 28 at 4 h p.i. for [Br-76]FLB 457, owing to a continuous wash out from the cerebellum. For [Br-76]FLB 463 the corresponding value increased from 10 to 19.5. [Br-76]FLB 457 has in contrast to [Br-76]FLB 463 a high uptake in thalamic structures and has therefore an additional potential as a radioligand for PET examination of extrastriatal dopamine D-2 receptors in the living human brain.