The Korean Journal of Nuclear Medicine (대한핵의학회지)

The Korean Society of Nuclear Medicine (대한핵의학회)
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N-(4-[$^{18}F$]Fluoromethylbenzyl)spiperone : A Selective Radiotracer for In Vivo Studies of Dopamine $D_2$ Receptors

N-(4-[$^{18}F$Fluoromethylbenzyl)spiperone : 유력한 도파민 $D_2$ 수용체 선택성 방사성리간드

  • Kim, Sang-Eun (Department of Nuclear Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center) ;
  • Choe, Yearn-Seong (Department of Nuclear Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center) ;
  • Chi, Dae-Yoon (Department of Chemistry, Inha University) ;
  • Lee, Kyung-Han (Department of Nuclear Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center) ;
  • Choi, Yong (Department of Nuclear Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center) ;
  • Kim, Byung-Tae (Department of Nuclear Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center)
  • 김상은 (성균관대학교 의과대학 삼성서울병원 핵의학과) ;
  • 최연성 (성균관대학교 의과대학 삼성서울병원 핵의학과) ;
  • 지대윤 (인하대학교 이과대학 화학과) ;
  • 이경한 (성균관대학교 의과대학 삼성서울병원 핵의학과) ;
  • 최용 (성균관대학교 의과대학 삼성서울병원 핵의학과) ;
  • 김병태 (성균관대학교 의과대학 삼성서울병원 핵의학과)
  • Published : 1997.11.20
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Abstract

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

[$^{18}F$]FMBS는 도파민 $D_2$ 수용체 방사성추적자로서 유망한 성질을 지니고 있다. [$^{18}F$]FMBS는 비교적 높은 특이결합/비특이결합 비를 제공하며, 그 체내결합은 도파민 $D_2$ 수용체에 대하여 높은 특이성과 선택성을 보인다. 도파빈 $D_2$ 수용체 측정을 위한 보다 적합한 PET 방사성추적자를 얻기 위해서는 [$^{18}F$]FMBS의 낮은 뇌섭취와 느린 역학을 개선할 수 있는 화학적 구조의 변형이 시도되어야 하며, [$^{18}F$]FMBS는 이러한 시도의 골격이 될 수 있을 것으로 믿는다.

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