Arnett C D, Fowler J S, Wolf A P, Shiue C Y, McPherson D W
Life Sci. 1985 Apr 8;36(14):1359-66. doi: 10.1016/0024-3205(85)90041-4.
N-Methylspiroperidol, the amide N-methyl analogue of the neuroleptic spiroperidol, was radiolabeled with fluorine-18, and its distribution in the baboon brain was studied using positron emission transaxial tomography. Stereospecific binding was demonstrated in the striatum (but not in the cerebellum) by pretreatment with (-)- or (+)-butaclamol. The kinetic distribution was similar to that of [18F]spiroperidol, but the absolute striatal uptake (in percent of administered dose) was at least two-fold higher. Analysis of baboon blood at 10 min after injection indicated that less than half of the radioactivity in the plasma was due to unchanged radioligand. Analysis of the metabolic stability of [18F]-N-methylspiroperidol in rat brain for 4 hr indicated that, like [18F]spiroperidol, it is very stable to metabolic transformation in the rat central nervous system. Striatal uptake and retention in the rat was five-fold higher for [18F]-N-methylspiroperidol than for [18F]spiroperidol. These results suggest that [18F]-N-methylspiroperidol is an ideal choice for studies of the dopamine receptor in humans.
N-甲基螺哌啶醇，即抗精神病药物螺哌啶醇的酰胺N-甲基类似物，用氟-18进行放射性标记，并使用正电子发射断层扫描研究其在狒狒脑中的分布。通过用（-）-或（+）-布他拉莫预处理，在纹状体（而非小脑）中证明了立体特异性结合。动力学分布与[18F]螺哌啶醇相似，但纹状体的绝对摄取量（占给药剂量的百分比）至少高出两倍。注射后10分钟对狒狒血液的分析表明，血浆中不到一半的放射性是由于未变化的放射性配体。对[18F]-N-甲基螺哌啶醇在大鼠脑中4小时的代谢稳定性分析表明，与[18F]螺哌啶醇一样，它在大鼠中枢神经系统中对代谢转化非常稳定。[18F]-N-甲基螺哌啶醇在大鼠中的纹状体摄取和保留量比[18F]螺哌啶醇高五倍。这些结果表明，[18F]-N-甲基螺哌啶醇是研究人类多巴胺受体的理想选择。
