In vivo labeling of the dopamine D2 receptor with N-11C-methyl-benperidol.
A new dopamine D2 receptor radiotracer, N-11C-methyl-benperidol (11C-NMB), was prepared and its in vivo biologic behavior in mice and a baboon was studied. Carbon-11-NMB was determined to bind to specific sites characterized as dopamine D2 receptors. The binding was saturable, reversible, and stereospecific. Kinetic studies in the dopamine D2 receptor-rich striatum showed that 11C-NMB was retained five times longer than in receptor-devoid regions, resulting in a high maximum striatal-to-cerebellar ratio of 11:1 at 60 min after injection. From frontal cortex and cortex, on the other hand, the tracer washed out as rapidly as it did from cerebellum, resulting in tissue-to-cerebellar ratios close to one in these regions at any time after injection. Blocking studies confirmed the specificity and selectivity of the 11C-NMB binding to the dopamine D2 receptor. A PET study with 11C-NMB of the baboon brain revealed highly selective labeling of dopamine D2 receptor sites which was blocked by preinjection of raclopride.
Suehiro
M
M
Div. of Nuclear Medicine and Radiation Health Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21205-2179.
Dannals
R F
RF
Scheffel
U
U
Stathis
M
M
Wilson
A A
AA
Ravert
H T
HT
Villemagne
V L
VL
Sanchez-Roa
P M
PM
Wagner
H N
HN
D000818:Animals; D001544:Benperidol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D008297:Male; D051379:Mice; D010215:Papio; D011485:Protein Binding; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C066786:N-methylbenperidol; D001544:Benperidol