@misc{oai:repo.qst.go.jp:00070528,
 author = {Takano, Harumasa and Ito, Hiroshi and Kimura, Yasuyuki and Seki, Chie and Suhara, Tetsuya and 高野 晴成 and 伊藤 浩 and 木村 泰之 and 関 千江 and 須原 哲也},
 month = {Sep},
 note = {Introduction: Positron emission tomography (PET) has enabled us to directly explore the pharmacokinetics of radiolabeled drugs in the living human body. Sulpiride, which is a benzamide derivative, is a dopamine D2 receptor antagonist and has been widely used as a psychotropic drug since the 1970's. Although sulpiride is known to have low brain penetration possibly due to its low lipophilicity, 50% of dopamine D2 receptor in the brain was occupied by an oral administration of sulpiride (500mg) in previous PET studies with selective dopamine D2 receptor radioligands such as [11C]raclopride and [11C]FLB457. In the present study, we injected [11C]sulpiride to healthy men to directly examine the distribution of [11C]sulpiride. In addition, we tested whether an oral administration of clinical dose of sulpiride would affect the distribution of [11C]sulpiride since the drug is reported to be a substrate of membrane transporters. Methods: Two young healthy men participated in this study. Thirty minutes after intravenous injection of [11C]sulpiride, whole body static images were obtained from head to thighs (8 bed positions with 3 min for each bed position) in a three-dimensional mode with a PET/computed tomography (CT) system. Furthermore, we performed PET scans 3 hours after an oral administration of a clinical dose of non-radiolabeled sulpiride (500 mg) with the identical scan protocol on the same day. Volumes of interest were manually delineated with reference to their CT images. The ratio of radioactivity to the injected dose for each organ (percent injected dose) was calculated and used as an index of distribution. Results: At baseline, high accumulation of the tracer was observed in the liver, gallbladder, intestine, kidney, and urinary tract, while very low accumulation was observed in the brain with the exception of the pituitary. After the oral administration of sulpiride, the accumulation of the tracer in the brain did not show any significant change from the baseline (from 0.2% to 0.2 %), whereas that in the liver showed a marked reduction from 12.6% to 5.0% on average. Discussion: At baseline, the low accumulation in the brain and high accumulation in the pituitary indicate the low penetration of sulpiride in the brain. In the other organs, a high accumulation in the liver, gallbladder, kidney and urinary tract indicate the fact that sulpiride is eliminated through both bile and urine. After administrating a clinical dose of sulpiride, we found no difference in the accumulation in the brain compared to the baseline, which indicates that more concentration is required to alter the function of efflux transporters in the blood brain barrier such as P-glycoprotein. In contrast, we found a difference in the accumulation in the liver. One possible explanation is that the non-radiolabeled sulpiride might compete with [11C]sulpiride at the organic cation transporter (OCT1) in the liver and therefore hamper the uptake of [11C]sulpiride. Further studies with a larger sample size are required to investigate the time course of distribution of [11C]sulpiride. In addition, a focused study on the brain penetration of sulpiride is also needed., World Molecular Imaging Congress 2011},
 title = {The distribution of [11C]sulpiride in humans and the effect of an oral administration of clinical dose of sulpiride: A preliminary positron emission tomography study},
 year = {2011}
}