IN-VIVO QUANTIFICATION OF HUMAN PULMONARY BETA-ADRENOCEPTOR DENSITY USING PET - COMPARISON WITH IN-VITRO RADIOLIGAND BINDING

A new method has recently been developed to quantify pulmonary beta-ad renergic receptors in vivo using PET. This study used in vitro radioli gand binding assay (PLEA) as the gold standard to validate in vivo PET measurements. Methods: Five male patients with lung cancer aged 57 yr (range 42-67 yr) were studied. PET scanning was performed the day bef ore thoracotomy to determine regional pulmonary beta-receptor density. RLBA was carried out on cell membranes prepared from specimens of lun g tissue obtained at the thoracotomy to measure beta-receptor density in vitro. In both cases, the hydrophilic nonselective beta-antagonist radioligand (S)-CGP-12177 was used. For PET studies, this was labeled with C-11 and for RLBA with H-3. Results: In the PET study, beta-recep tor density (B-max) was 9.43 +/- 1.32 pmole g(-1) tissue. In the RLBA study, B-max was 99.0 +/- 15.5 fmole mg(-1) protein, equivalent to 9.9 0 +/- 1.55 pmole g(-1) tissue. These values are in good agreement with previously reported in vitro measurements on human lung membranes usi ng I-125-iodocyanopindolol. A correlation was found between beta-adren ergic density obtained using PET and beta-adrenergic density obtained using RLBA (r = 0.92; p < 0.05). Conclusion: The results support the u se of PET as a new method for imaging and quantifying pulmonary beta-a drenergic receptors in vivo, opening the way for studies of physiologi cal and pharmacological regulation of beta-adrenergic receptors throug h noninvasive serial measurements.