PET imaging studies of dopamine D2 receptors: comparison of [18F]N-methylspiperone and the benzamide analogues [18F]MABN and [18F]MBP in baboon brain.
A series of positron emission tomography (PET) imaging studies was conducted in a baboon with the benzamide derivatives [18F]2,3-dimethoxy-N-[9-(4-fluorobenzyl)-9-azabicyclo[3.3.1]non an-3 beta-yl]benzamide ([18F]MABN) and [18F]2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl]be nza mide ([18F]MBP). Studies were also conducted with the butyrophenone [18F]N-methylspiperone (NMSP) for comparison. Tissue-time activity curves of [18F]MABN are similar to those of [18F]NMSP since both compounds displayed approximately the same uptake in the basal ganglia and displayed irreversible binding kinetics in vivo. However, the rapid rate of clearance from the cerebellum and high basal ganglia:cerebellum ratio of [18F]MABN indicate that this compound has a much lower amount of nonspecific binding than [18F]NMSP. [18F]MBP displayed a higher uptake in the basal ganglia relative to [18F]NMSP and [18F]MABN and exhibited reversible binding kinetics in vivo. This property of [18F]MBP is desirable since the uptake of radioactivity in D2-rich ligands is less likely to be influenced by changes in cerebral blood flow. The current data suggest that both [18F]MABN and [18F]MBP are promising ligands for studying dopamine D2 receptors with PET.
Mach
R H
RH
Cerebrovascular Research Center, University of Pennsylvania, Philadelphia 19104, USA.
Ehrenkaufer
R L
RL
Greenberg
J H
JH
Shao
L
L
Morton
T E
TE
Evora
P H
PH
Nowak
P A
PA
Luedtke
R R
RR
Cohen
D
D
Reivich
M
M
D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005260:Female; D005462:Fluorine Radioisotopes; D010215:Papio; D010880:Piperidines / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005462:Fluorine Radioisotopes; D010880:Piperidines; D017448:Receptors, Dopamine D2; C084477:2,3-dimethoxy-N-(1-(4-fluorobenzyl)piperidin-4-yl)benzamide; D013134:Spiperone; C039167:3-N-methylspiperone; C084478:2,3-dimethoxy-N-(9-(4-fluorobenzyl)-9-azabicyclo(3.3.1)nonan-3-yl)benzamide