title: Evaluation of 75Br-labelled butyrophenone neuroleptics for imaging cerebral dopaminergic receptor areas using positron emission tomography.
abstract: 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 (T1/2 = 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 striatum-to-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.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D001544:Benperidol / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001966:Bromine; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives / Q000378:metabolism; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis*; D013134:Spiperone / Q000031:analogs & derivatives / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D011868:Radioisotopes; D011954:Receptors, Dopamine; D013134:Spiperone; C026326:4-bromospiperone; C042942:brombenperidol; D001544:Benperidol; D006220:Haloperidol; C006820:bromperidol; D001966:Bromine