Characterization of pulmonary and myocardial beta-adrenoceptors with S-1'-[fluorine-18]fluorocarazolol.
S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its potential for noninvasive measurement of regional pulmonary and myocardial beta-adrenoceptor densities.


METHODS
High-specific activity fluorocarazolol was intravenously injected on two separate occasions within a 1-wk interval. The initial injection was without pretreatment, but before the second injection, the volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time frames of 31 planes were acquired over a period of 60 min after each injection. Blood samples were drawn and analyzed for the presence of fluorocarazolol and radioactive metabolites.


RESULTS
Uptake of fluorocarazolol in the target tissues was hardly affected by salbutamol but was strongly depressed by pindolol. Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50 min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after treatment with pindolol.


CONCLUSIONS
These data indicate that: 1. Pulmonary and myocardial uptake of radioactivity after intravenous administration of S-1'-[18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2. Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle under these conditions. 3. Binding kinetics do not preclude quantification of receptors with compartment models.
Visser
T J
TJ
Positron Emission Tomography Center, University Hospital, Groningen, The Netherlands.
van Waarde
A
A
van der Mark
T W
TW
Kraan
J
J
Elsinga
P H
PH
Pruim
J
J
Ensing
K
K
Jansen
T
T
Willemsen
A T
AT
Franssen
E J
EJ
Visser
G M
GM
Paans
A M
AM
Vaalburg
W
W
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000328:Adult; D000420:Albuterol; D002227:Carbazoles / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008024:Ligands; D008168:Lung / Q000737:chemistry* / Q000000981:diagnostic imaging; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D010869:Pindolol; D011412:Propanolamines / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D014055:Tomography, Emission-Computed
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005462:Fluorine Radioisotopes; D008024:Ligands; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C089702:fluorocarazolol; D010869:Pindolol; D000420:Albuterol