Positron emission tomography studies of human airways using an inhaled beta-adrenoceptor antagonist, S-11C-CGP 12388.

Objectives: 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.

PET imaging of beta-adrenoceptors in human brain: a realistic goal or a mirage?

Beta-adrenoceptors are predominantly located in the cerebral cortex, nucleus accumbens and striatum. At lower densities, they are also present in amygdala, hippocampus and cerebellum. Beta-2 sites regulate glial proliferation during ontogenic development, after trauma and in neurodegenerative diseases.

Quantification of beta-adrenoceptor density in the human heart with (S)-[11C]CGP 12388 and a tracer kinetic model.

The aim of this study was to determine whether the beta-adrenoceptor receptor density (Bmax) and the ligand affinity (KD) of (S)-[11C]CGP 12388 for the beta-adrenoceptor receptor could be determined using full tracer kinetic modelling of the transport of the ligand and its interaction with the receptor. This approach minimises the a priori assumptions and may thus serve as a gold standard to validate other simplified methods. Dynamic positron emission tomography (PET) data were acquired in six healthy subjects during 60 min.

Synthesis and evaluation of (S)-[18F]-fluoroethylcarazolol for in vivo beta-adrenoceptor imaging in the brain.

The beta-adrenergic receptor ligand (S)-4-(3-(2'-[18F]-fluoroethylamino)-2-hydroxypropoxy)-carbazol ((S)-[18F]-fluoroethylcarazolol) was prepared by reaction of [18F]-fluoroethylamine with the corresponding (S)-epoxide and was evaluated in rats by studying its pharmacokinetics and its binding profile both in vitro and in vivo. In vitro, (S)-fluoroethylcarazolol binds preferentially to beta-adrenoceptors (pK(i)=9.3 for beta(1) and 9.

Imaging of beta-adrenoceptors in the human thorax using (S)-[(11)C]CGP12388 and positron emission tomography.

We report positron emission tomography studies of beta-adrenoceptors in the human thorax with (S)-[(11)C]CGP12388 (4-(3-(2'-[(11)C]-isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one). Beta-adrenoceptors have previously been quantified using (S)-[(11)C]CGP12177 (4-(3-tert-butylamino-2-hydroxypropoxy)-2H-benzimidazol-2[(11)C]-one), but (S)-[(11)C]CGP12388 is more easily prepared and therefore more suitable in a clinical setting. (S)-[(11)C]CGP12388 was administered to five healthy volunteers on two separate days (control and pindolol block study).