title: In vivo quantification of pulmonary beta-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET.
abstract: The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 [(S)-[11C]CGP-12177] and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), C15O (blood volume), and (S)-[11C]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[11C]-CGP-12177 (7.1 +/- 2.0 micrograms, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[11C]CGP-12177 injection (34.0 +/- 4.8 micrograms, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.
authors.affiliation: Medical Research Council Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Ueki
authors.forename: C G
authors.initials: CG
authors.lastname: Rhodes
authors.forename: J M
authors.initials: JM
authors.lastname: Hughes
authors.forename: R
authors.initials: R
authors.lastname: De Silva
authors.forename: D C
authors.initials: DC
authors.lastname: Lefroy
authors.forename: P W
authors.initials: PW
authors.lastname: Ind
authors.forename: F
authors.initials: F
authors.lastname: Qing
authors.forename: F
authors.initials: F
authors.lastname: Brady
authors.forename: S K
authors.initials: SK
authors.lastname: Luthra
authors.forename: C J
authors.initials: CJ
authors.lastname: Steel
mesh_terms: D000319:Adrenergic beta-Antagonists; D000328:Adult; D001810:Blood Volume / Q000502:physiology; D002250:Carbon Radioisotopes; D006332:Cardiomegaly / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D015633:Extravascular Lung Water / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011412:Propanolamines; D011652:Pulmonary Circulation / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C033394:CGP 12177