氟-18标记的吡啶基哒螨灵类似物的合成及生物性能

doi:10.3969/j.issn.1006-7795.2013.01.003

首都医科大学学报 ›› 2013, Vol. 34 ›› Issue (1): 11-17.doi: 10.3969/j.issn.1006-7795.2013.01.003

氟-18标记的吡啶基哒螨灵类似物的合成及生物性能

牟甜甜¹, 张现忠², 王蒨¹, 彭程³, 马云川³, 米宏志¹

1. 首都医科大学附属北京安贞医院核医学科, 北京 100029;
2. 厦门大学公共卫生学院分子影像暨转化医学研究中心, 厦门 361005;
3. 首都医科大学附属宣武医院PET中心, 北京 100053

收稿日期:2012-12-06 出版日期:2013-02-21 发布日期:2013-02-25
通讯作者: 张现忠, 王蒨 E-mail:zhangxzh@hotmail.com;13801043425@vip.sina.com
基金资助:
国家自然科学基金(20871020, 81271613, 21271030);北京市自然科学基金(2092018)资助项目。

Synthesis and biodistribution of ¹⁸F-labeled pyridyl pyridaben analogues

MOU Tiantian¹, ZHANG Xianzhong², WANG Qian¹, PENG Cheng³, MA Yunchuan³, MI Hongzhi¹

1. Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China;
2. Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361005, China;
3. PET Center of Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2012-12-06 Online:2013-02-21 Published:2013-02-25
Supported by:
This study was supported by National Natural Science Foundation of China (20871020, 81271613, 21271030) and Natural Science Foundation of Beijing (2092018).

摘要/Abstract

摘要：

目的设计并合成一种氟-18标记的哒螨灵类似物:4-氯-2-叔丁基-5-[6-[4-[2-[2-[2-氟[¹⁸F]乙氧基]乙氧基]乙氧基]-1H-1,2,3-三唑-1-基]甲基]-2-吡啶基]甲氧基]-3(2H)-哒嗪酮 ([¹⁸F]FPTP-P3),并评价其用于心肌灌注显像的可能性。方法采用[¹⁸F]F^-取代OTs前体的方法进行标记,通过稳定性研究、脂水分配系数测定、生物分布实验等手段对标记物进行评价。结果 [¹⁸F]FPTP-P3的总制备时间为70~90 min,校正后的放化产率为36±5.6%,放化纯>98%。[¹⁸F]FPTP-P3为脂溶性化合物,在水溶液中可稳定放置3 h以上。生物分布实验结果显示,[¹⁸F]FPTP-P3在小鼠心肌具有一定的初始摄取,且肝部清除较快,但其心肌滞留较差。结论 [¹⁸F]FPTP-P3不具有用于心肌显像的潜力。

关键词: [¹⁸F]FPTP-P3, 哒螨灵, 心肌摄取, 生物分布

Abstract:

Objective A fluorine-18 labeled pyridazinone derivative: 4-chloro-2-tert-butyl-5-[6-[4-[2-[2-[2-[¹⁸F]fluroethoxy]ethoxy]ethoxy]-1H-1,2,3-triazol-1-yl]methyl]-2-pyridinyl]methoxy]-3(2H)-pyridazinone ([¹⁸F]FPTP-P3) was designed and prepared, and its potential as a myocardial perfusion imaging agent was evaluated. Methods [¹⁸F]FPTP-P3 was prepared by substituting tosyl of precursor with ¹⁸F. The tracer was evaluated by stability study, octanol/water partition coefficient and biodistribution study. Results The total radio-synthesis time was 70-90 min, typical decay-corrected radiochemical yield was 36±5.6%, and the radiochemical purity (RCP) was>98% after purification. It is a lipophilic compound, and stable in water for 3 h. The results of biodistribution study in mice showed that [¹⁸F]FPTP-P3 had certain initial heart uptake and the clearance of liver was very fast as well. However the retention of heart uptake was not ideal.Conclusion [¹⁸F]FPTP-P3 is not suitable for heart imaging in vivo.

Key words: [¹⁸F]FPTP-P3, pyridaben, heart uptake, biodistribution

中图分类号:

R392
Q2

牟甜甜, 张现忠, 王蒨, 彭程, 马云川, 米宏志. 氟-18标记的吡啶基哒螨灵类似物的合成及生物性能[J]. 首都医科大学学报, 2013, 34(1): 11-17.

MOU Tiantian, ZHANG Xianzhong, WANG Qian, PENG Cheng, MA Yunchuan, MI Hongzhi. Synthesis and biodistribution of ¹⁸F-labeled pyridyl pyridaben analogues[J]. Journal of Capital Medical University, 2013, 34(1): 11-17.

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氟-18标记的吡啶基哒螨灵类似物的合成及生物性能

Synthesis and biodistribution of ¹⁸F-labeled pyridyl pyridaben analogues

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氟-18标记的吡啶基哒螨灵类似物的合成及生物性能

Synthesis and biodistribution of 18F-labeled pyridyl pyridaben analogues

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Synthesis and biodistribution of ¹⁸F-labeled pyridyl pyridaben analogues