IN-VIVO QUANTIFICATION OF PULMONARY BETA-ADRENOCEPTOR DENSITY IN HUMANS WITH (S)-[C-11]CGP-12177 AND PET

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)-[C-11]CGP-121771 and positron emission tomography (PET). Six normal male volunteers an d eight patients with hypertrophic cardiomyopathy were studied. PET sc anning consisted of transmission (tissue density), (CO)-O-15 (blood vo lume), and (S)-[C-11]CGP-12177 (beta-adrenoceptor) emission scans. Hig h-specific-activity (S)-[C-11]CGP-12177 (7.1 +/- 2.0 mug, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[C-11]CGP12177 injection (34.0 +/- 4.8 mug, 2.3 +/- 0.8 GBq/mumol ). Binding capacity (Bmax) was calculated in each region of interest a s picomoles per gram by normalizing it to the local extravascular tiss ue density. In normal subjects, average Bmax for all regions of intere st was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously report ed in vitro values. In both groups there were no differences in beta-a drenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, e xtravascular tissue density was 24% higher than in normal subjects; Bm ax per milliliter thoracic volume was correspondingly higher but was n ot different from that in normal subjects when expressed per gram tiss ue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoc eptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.