Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.
We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier.


METHODS
The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode.


RESULTS
Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals.


CONCLUSIONS
Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.
van Waarde
A
A
Department of Neurology, University Hospital, Groningen, The Netherlands.
Visser
T J
TJ
Elsinga
P H
PH
de Jong
B
B
van der Mark
T W
TW
Kraan
J
J
Ensing
K
K
Pruim
J
J
Willemsen
A T
AT
Brodde
O E
OE
Visser
G M
GM
Paans
A M
AM
Vaalburg
W
W
D000319:Adrenergic beta-Antagonists; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002227:Carbazoles; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D010869:Pindolol; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D014055:Tomography, Emission-Computed
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005462:Fluorine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C089702:fluorocarazolol; D010869:Pindolol