三种碳-11标记的苯乙胺衍生物的合成与生物分布研究

通过氨基甲基化的方法用碳-11甲基标记了N-甲基苯乙胺、N-甲基间羟基苯乙胺和N-甲基酪胺三种化合物,评价了放射性核素标记的三种化合物在昆明小鼠体内的生物分布特征。合成结果显示,11 C]-N-甲基苯乙胺合成包括HPLC分离总耗时约30min,放化产率为25%、放化纯度98%,11 C]-N-甲基间羟基苯乙胺合成包括HPLC分离总耗时约25min,放化产率为13%、放化纯度97%,11 C]-N-甲基酪胺合成包括HPLC分离总耗时约25min,放化产率为28%、放化纯度98%;小鼠体内生物分布结果显示:三个标记物在各测定时间点小鼠靶器官心肌的摄取均比肺、肝、脾、肾等非靶器官的摄取低,心肌摄取与肌肉摄取相近。注射后10min时11 C]-N-甲基苯乙胺的心与肺放射性摄取比为1/2.08、心与肝为1/2.94,11 C]-N-甲基间羟基苯乙胺的心与肺放射性摄取比为1/2.56、心与肝为1/2.76,11 C]-N-甲基酪胺的心与肺放射性摄取比为1/1.85、心与肝为1/5。以上结果提示,碳-11甲基标记N-甲基苯乙胺、N-甲基间羟基苯乙胺和N-甲基酪胺的合成方法虽然简单,但是心肌靶向性差,不适用于核素心肌显像。

Synthesis and Bio-distribution of Three Carbon-11-Labeled Phenylethylamine Derivatives

N-methylphenylethylamine,N-m-MeTyramine and N-P-MeTyramine were labeled with Carbon-11 by methylation of amino group.Biological distribution characteristics of the three radiolabeled compounds in Kunming mice were evaluated.Synthesis of 11 C]-N-methylphenethylamine requires 30 minutes including HPLC separation time.The yield was 25％ and the radiochemical purity was more than 98％.Synthesis of 11 C]m-MeTyramine required 25 minutes including HPLC separation time.The yield was 13％ and the radiochemical purity was more than 97％.Synthesis of 11C] P-MeTyramine required 25 minutes including HPLC separation time.The yield was 28％ and the radiochemical purity was more than 98％.Distribution study showed that amount of the three marker uptaken by the target organism-myocardium,at each time point was smaller than that uptaken by non-target organs like lung,liver,spleen,kidney.Myocardial uptake was similar with that of muscle.After injection of the markers for 10 minutes,concentration of 11C]-N-methylphenethylamine in lung and liver was 2.08 and 2.94 times higher than that in heart,respectively.Concentration of 11C]m-MeTyramine in lung and liver was 2.56,2.76 higher than that in heart,respectively.Concentration of 11C]P-MeTyramine in lung and liver was 1.85 and 5 higher than that in heart,respectively.Present results suggested that although synthetic methods of 11C labeled N-methylphenylethylamine,N-m-MeTyramine and N-P-MeTyramine were simple,but the targeting in myocardium were poor and might not be suitable for myocardial perfusion imaging.