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In vivo quantification of human pulmonary beta-adrenoceptor density using PET: comparison with in vitro radioligand
F Qing1, C G Rhodes, M J Hayes
1MRC Clinical Sciences Center, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Unlabelled:
A new method has recently been developed to quantify pulmonary beta-adrenergic receptors in vivo using PET. This study used in vitro radioligand binding assay (RLBA) 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 before thoracotomy to determine regional pulmonary beta-receptor density. RLBA was carried out on cell membranes prepared from specimens of lung 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 11C and for RLBA with 3H.
Results:
In the PET study, beta-receptor density (Bmax) was 9.43 +/- 1.32 pmole g-1 tissue. In the RLBA study, Bmax was 99.0 +/- 15.5 fmole mg-1 protein, equivalent to 9.90 +/- 1.55 pmole mg-1 tissue. These values are in good agreement with previously reported in vitro measurements on human lung membranes using 125I-iodocyanopindolol. A correlation was found between beta-adrenergic density obtained using PET and beta-adrenergic density obtained using RLBA (r = 0.92; p < 0.05).
Conclusion:
The results support the use of PET as a new method for imaging and the way for studies of physiological and pharmacological regulation of beta-adrenergic receptors through noninvasive serial measurements.