TY - JOUR
T1 - Evaluation of 75Br-labelled butyrophenone neuroleptics for imaging cerebral dopaminergic receptor areas using positron emission tomography
AU - Moerlein, Stephen M.
AU - Laufer, Peter
AU - Stöcklin, Gerhard
AU - Pawlik, Günter
AU - Wienhard, Klaus
AU - Heiss, Wolf Dieter
PY - 1986/8
Y1 - 1986/8
N2 - 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 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.
AB - 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 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.
KW - Br
KW - Brombeperidol
KW - Bromospiperone
KW - Bromperidol
KW - Butyrophenone neuroleptic
KW - Cerebral dopaminergic receptors
KW - Postron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=0022555488&partnerID=8YFLogxK
U2 - 10.1007/BF00256924
DO - 10.1007/BF00256924
M3 - Article
C2 - 2876896
AN - SCOPUS:0022555488
SN - 0340-6997
VL - 12
SP - 211
EP - 216
JO - European Journal of Nuclear Medicine
JF - European Journal of Nuclear Medicine
IS - 4
ER -