Synthesis of High Specific Activity [⁷⁵Br]-and [⁷⁷Br]Bromperidol and Tissue Distribution Studies in the Rat

A rapid synthesis of [⁷⁶Br]-and [⁷⁷Br]bromperidol with specific activity exceeding 10000 Ci/mmol is described in which a trimethylstannylated analogue of bromperidol is used as a substrate for regiospecific no-carrier-added radiobromination. 4-[4-[4-(Trimethylstannyl)phenyl]-4-hydroxypiperidino]-4'-fluorobutyrophenone was synthesized by the reaction of (trimethylstannyl)sodium with haloperidol and purified by preparative HPLC. Subsequent radiobromination with no-carrier-added ⁷⁵Br^-or ⁷⁷Br^-and in situ oxidation using H₂O₂/CH₃COOH gave a corrected radiochemical yield of 35% with a 30-min preparation time. Tissue distribution studies in the rat show a rapid and prolonged uptake into the brain, liver, and kidneys and consistently low blood concentrations that differ quantitatively from previous studies using relatively low specific activity bromperidol. Potential clinical applications for this high specific activity radiobrominated neuroleptic are discussed.