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 [C-11] (+)McN5652, a radioligand for serotonin transporter (5-HTT), and inactive enantiomer [C-11](-)McN5652 in 19 healthy men (12 nonsmokers and 7 smokers) using positron emission tornography. Pretreatment study was performed by the administration of clomipramine (50mg), a potent 5-HTT inhibitor. Results The mean lung uptake of [C-11](+)McN5652 and [C-11](-)McN5652 was significantly higher in smokers than in nonsmokers. The lung uptake of [C-11](+)McN5652 decreased after pretreatment with clomipramine, whereas that of [C-11](-)McN5652 was not affected by clomipramine. Conclusions Lung uptake of [C-11](-)McN5652 was influenced by smoking, possibly because the probable nonspecific binding accumulation was changed as [C-11] (-)McN5652 was reported to have negligible affinity to 5-HTT. Smoking might be one of the important factors when distribution of radioligands is considered.