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 ^(18)F-labeled pyridyl pyridaben analogues

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。

Objective A fluorine-18 labeled pyridazinone derivative： 4-chloro-2-tert-butyl-5-[6-[4-[2-[2-[2-[18^F]fluroethoxy]ethoxy]ethoxy]-1H-1,2,3-triazol-1-yl]methyl]-2-pyridinyl]methoxy]-3（2H）-pyridazinone （[18^F]FPTP-P3） was designed and prepared, and its potential as a myocardial perfusion imaging agent was evaluated. Methods [18^F]FPTP-P3 was prepared by substituting tosyl of precursor with 18^F. 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 [18^F]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 [18^F]FPTP-P3 is not suitable for heart imaging in vivo.