Evaluation of 75Br-labelled butyrophenone neuroleptics for imaging cerebral dopaminergic receptor areas using positron emission tomography

A comparative evaluation of three radiobrominated butyrophenone neuroleptics — bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP) — was made to assess the applicability of these compounds as radiopharmaceuticals labelled with the positron emitter ⁷⁵Br (T_1/2=1.6 h) for mapping cerebral dopaminergic receptor areas non-invasively with positron emission tomography (PET). BSP, BBP, and BP were prepared in high specific activities with high radiochemical yields, using electrophilic reactions with no-carrier-added ⁷⁷Br^- or ⁷⁵Br^-. Screening tests in rats using ⁷⁷Br-labelled compounds indicated D₂-specific localization for ⁷⁷Br-BSP and ⁷⁷Br-BBP, whereas PET experiments in baboons showed that only ⁷⁵Br-BSP preferentially localized in cerebral tissues rich in dopaminergic receptors. The data suggest an inverse relationship between cerebral uptake and receptor-specific localization, which was attributed to a complicated interplay between the D₂ receptor binding affinity, lipophilicity, % ionization and molecular weight of the radioligand, and the binding capacity of the cerebral tissues. ⁷⁵Br-BSP gave a striatumto-cerebellum ratio of 3 in baboon brain 5 h post-injection, which allowed visualization of dopaminergic-receptor-containing areas of the living brain using PET.