• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine >Automated Chemoenzymatic Synthesis of No-carrier-added [carbonyl-↑(11]C]Propionyl L-Carnitine for Pharmacokinetic Studies
【24h】

Automated Chemoenzymatic Synthesis of No-carrier-added [carbonyl-↑(11]C]Propionyl L-Carnitine for Pharmacokinetic Studies

机译：自动化学合成无载体的[羰基-↑（11] C]丙酰基L-肉碱的药代动力学研究

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-ll (t↓(12), = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [↑(11)C]propionyl chloride as labelling agent via ↑(11)C-carboxylation of ethylmagnesium bromide with cyclotron-produced [↑(11)C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [↑(11)C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [↑(11)C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [↑(11)C]carbon dioxide. However. the radiosynthesis was unsuccessful at the no-carrier-added (NCA) level of specific radioactivity. [↑(ll)C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [↑(11)C]carbon dioxide and hydrolysis. NCA [↑(11)C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [↑(11)C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [↑(11)C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [↑(11)C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [↑(11)C]PLC in high radioactivities ready For intravenous administration within 25 min from radionuclide production. The [↑(11)C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo.#1997 Elsevier Science Ltd
机译：丙酰基左旋肉碱（PLC）正在开发中，用于治疗周围动脉疾病，冠心病和慢性心力衰竭。研究了三种方法，分别用发射正电子的碳-II（t↓（12），= 20.3分钟），一种化学试剂和两种化学酶标记丙酸酯中的PLC。前者的基础是通过乙基溴化镁的↑（11）C-羧化与回旋加速器产生的[↑（11）C]二氧化碳并随后进行氯化来制备[↑（11）C]丙酰氯作为标记剂。在三氟乙酸中，添加了载体的[↑（11）C]丙酰氯与L-肉碱的反应，从回旋加速器产生的[↑（11）C ]二氧化碳。然而。在无放射性的特定放射性水平下，放射性合成未成功。通过化学溴化乙基镁镁与[↑（11）C]的二氧化碳羧化并水解，制备了作为化学酶途径的放射性前体的[↑（II）C]丙酸酯。 NCA [↑（11）C] PLC通过乙酸激酶，磷酸转乙酰基酶和肉碱乙酰基转移酶催化的连续转化，从[↑（11）C]丙酸酯中以14％的放射化学收率（校正衰减）制备了NCA [↑（11）C] PLC。基于新型支持的格氏试剂用于合成[↑（11）C]丙酸酯和S-乙酰-CoA合成酶和肉碱的转化，开发了NCA [↑（11）C] PLC的优良化学酶法合成方法乙酰转移酶。得到的总放射化学产率为30-48％（经衰减校正）。该合成自动化进行以确保放射安全，并提供了高放射性活度的纯NCA [↑（11）C] PLC，准备在放射性核素生产后25分钟内静脉内给药。 [↑（11）C] PLC适用于患有PET的人类受试者的药代动力学研究，并阐明体内PLC的丙酰基的命运。＃1997 Elsevier Science Ltd

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号