Effects of smoking on the lung accumulation of [11C]McN5652.
OBJECTIVE
The lung is one of the key organs for determining the distribution of drugs in the human body. Various factors influence the accumulation of drugs. In this study, we investigated the effects of smoking on drug distribution to the lung using radiolabeled drugs.


METHODS
We measured the lung uptake of [11C](+)McN5652, a radioligand for serotonin transporter (5-HTT), and inactive enantiomer [11C](-)McN5652 in 19 healthy men (12 nonsmokers and 7 smokers) using positron emission tomography. Pretreatment study was performed by the administration of clomipramine (50 mg), a potent 5-HTT inhibitor.


RESULTS
The mean lung uptake of [11C](+)McN5652 and [11C](-)McN5652 was significantly higher in smokers than in nonsmokers. The lung uptake of [11C](+)McN5652 decreased after pretreatment with clomipramine, whereas that of [11C](-)McN5652 was not affected by clomipramine.


CONCLUSIONS
Lung uptake of [11C](-)McN5652 was influenced by smoking, possibly because the probable nonspecific binding accumulation was changed as [11C](-)McN5652 was reported to have negligible affinity to 5-HTT. Smoking might be one of the important factors when distribution of radioligands is considered.
Takano
Akihiro
A
Clinical Neuroimaging Section, Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-8555, Japan.
Ito
Hiroshi
H
Sudo
Yasuhiko
Y
Inoue
Makoto
M
Ichimiya
Tetsuya
T
Yasuno
Fumihiko
F
Suzuki
Kazutoshi
K
Suhara
Tetsuya
T
D000328:Adult; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D012907:Smoking / Q000378:metabolism*
D007546:Isoquinolines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; C058079:McN 5652