Synthesis and biodistribution of ~(18)F-labeled pyridyl pyridaben analogues

Abstract

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-[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 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 [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.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~