Kawai K, Ohta H, Kubodera A, Channing M A, Eckelman W C
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Nucl Med Biol. 1996 Apr;23(3):251-5. doi: 10.1016/0969-8051(95)02054-3.
Regioselective radioiodination of N-trifluoroacetyl 3,4-dimethoxy-6-trifluoroacetoxymercurio-L-phenylalanine ethyl ester 1 under no-carrier-added condition gave 6-[125I]iodo protected L-DOPA with a labeling efficiency of more than 85%, and no-carrier-added 6-[125I]I-L-DOPA was obtained with a radio-chemical purity of over 95% after hydrolysis and chromatography. A nonradioactive standard of 6-iodo protected L-DOPA was synthesized by the iododemercuration of 6-mercuric trifluoroacetate protected L-DOPA 1 using I2 in chloroform. 6-[125I]I-L-DOPA showed high brain accumulation and rapid blood clearance in mice. The rat brain slice studies indicated high affinity of 6-[125I]I-L-DOPA for carrier-mediated and stereoselective active transport systems. The tissue homogenate analysis revealed that most of the accumulated radioactivity was intact 6-[125I]I-L-DOPA. Thus, 6-[123I]I-L-DOPA appears to be a suitable single photon emission computed tomography (SPECT) tracer for the selective measurement of cerebral L-amino acid transport, having no affinity for dopamine metabolism.
在无载体添加条件下，对N-三氟乙酰基-3,4-二甲氧基-6-三氟乙酰氧基汞-L-苯丙氨酸乙酯1进行区域选择性放射性碘化，得到标记效率超过85%的6-[125I]碘代保护的L-多巴，水解和色谱分离后得到放射化学纯度超过95%的无载体添加的6-[125I]I-L-多巴。通过在氯仿中用I2对6-三氟乙酸汞保护的L-多巴1进行脱汞碘化反应，合成了6-碘代保护的L-多巴的非放射性标准品。6-[125I]I-L-多巴在小鼠体内显示出高脑摄取和快速的血液清除。大鼠脑切片研究表明，6-[125I]I-L-多巴对载体介导的立体选择性主动转运系统具有高亲和力。组织匀浆分析显示，大部分积累的放射性是完整的6-[125I]I-L-多巴。因此，6-[123I]I-L-多巴似乎是一种适用于选择性测量脑L-氨基酸转运的单光子发射计算机断层扫描（SPECT）示踪剂，对多巴胺代谢无亲和力。
