Positron emission tomography studies of human airways using an inhaled beta-adrenoceptor antagonist, S-11C-CGP 12388.
OBJECTIVE
Positron emission tomography (PET) scanning may provide information on changes in the density and affinity of airway beta-adrenoceptors in lung diseases. However, the injection of a radiolabeled beta-blocker results in a pulmonary PET signal that reflects the binding of the ligand in the alveoli and not in the airways. Better discrimination between alveolar and airway beta-adrenoceptors may be possible with an inhaled radioligand.


METHODS
A nebulizer was used to administer the antagonist S-11C-CGP12388 in aerosol form. Eight volunteers inhaled the tracer twice, at baseline and after pretreatment with a beta-adrenergic drug. In both PET scan studies, a dynamic scan of the lungs was followed by a whole-body scan to assess the inhaled dose. Pulmonary uptake was quantified using a region-of-interest-based analysis.


METHODS
University hospital.


METHODS
Healthy volunteers.


METHODS
Pretreatment consisted either of inhaled salbutamol (400 microg, 20 min before the scan), or orally administered pindolol (3 x 5 mg during a period of 16 h before PET scanning).


RESULTS
Drug pretreatment did not affect pulmonary deposition of the radioligand. The agonist salbutamol accelerated the monoexponential washout of 11C not only in the peripheral lung (mainly alveoli), but also in the central lung (mainly airways) and in the main bronchi. An even larger increase of the washout rate was induced by the antagonist pindolol.


CONCLUSIONS
The similar effects of pindolol and salbutamol on tracer kinetics suggest that accelerated washout is due to the blockade of beta-adrenoceptors. Thus, the interaction of drugs with airway beta-adrenoceptors can be visualized using PET scanning and an inhaled radioligand.
van Waarde
Aren
A
Department of Internal Medicine & Molecular Imaging, University Medical Center of Groningen, PO Box 30001, 9700RB Groningen, Netherlands. a.van.waarde@pet.azg.nl
Maas
Bram
B
Doze
Petra
P
Slart
Riemer H
RH
Frijlink
Henderik W
HW
Vaalburg
Willem
W
Elsinga
Philip H
PH
D000280:Administration, Inhalation; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049628:Body Size; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D010869:Pindolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D012016:Reference Values; D012137:Respiratory System / Q000000981:diagnostic imaging* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002250:Carbon Radioisotopes; C109239:CGP 12388; D010869:Pindolol; D000420:Albuterol