188Re(CO)3Ln新型配合物的小鼠体内生物分布

夏姣云; 汪勇先; 于俊峰; 尹端沚

[¹⁸⁸Re(CO)₃L]_n新型配合物的小鼠体内生物分布

1.
长沙理工大学化学与环境工程学院, 长沙 410076
2.
中国科学院上海应用物理研究所放射性药物研究中心, 上海 201800

详细信息

通讯作者:
夏姣云

中图分类号: R811.5
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出版历程
- 收稿日期: 2007-07-01
- 修回日期: 2008-01-13
- 刊出日期: 2008-05-19

Biodistribution of Novel ¹⁸⁸Re-Tricarbonyl Complexes in Mice

1.
College of Chemistry and Environmental Engineering, Changsha University of Science and Technology, Changsha 410076, China
2.
China College of Radiopharmaceutical Center, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai 201800, China

More Information

Corresponding author:
XIA Jiao-yun

摘要

摘要: 选择了3种三齿配体(二(2-吡啶甲基)-胺基)-乙胺（L¹NH₂）、(二（2-吡啶甲基）-氨基)-乙酸（L²H）和((6-胺基-N-叔丁氧基羰基-己基)-吡啶-2-甲基氨基)-乙酸（L³NH₂），用于设计合成新的以 fac-[¹⁸⁸-Re(CO)₃]⁺为核心的放射性药物。3种配体在低浓度（10^-5 mol/L）的条件下，反应时间小于60 min，标记率可达90%以上，放射化学纯度大于92%；3种标记物的体外稳定性均很高，标记后24 h内基本不分解。生物分布结果表明，配合物均能较快地从血液和多数的组织器官中清除，主要通过排泄系统代谢，并初步探讨了这3个配合物在小鼠体内的生物分布行为可能与它们的脂水分配系数lg P有关。lg P值（-0.36）高的配合物[¹⁸⁸Re(CO)₃L₃NH₂]， 24 h时在各个器官中放射性保留均高于其它2个配合物，但可能不是唯一的影响因素。总的来说，3个配基是用fac-[¹⁸⁸Re(H₂O)₃(CO)₃]⁺标记的比较理想的双功能螯合剂。
- ¹⁸⁸Re /
- 双功能螯合剂 /
- 生物分布
Abstract: Three novel tridentate ligands (L¹NH₂= bis(2-pyridylmethyl)-amino)-ethylamine, L²H = bis(2-pyridylmethyl)-amino)-acetic acid, L³NH₂ = [(6-amino-hexyl)-pyridyl-2-methyl-amino]-acetic acid) were used as bifunctional chelating agents for the organometallic precursor fac-[¹⁸⁸Re (CO)₃(H₂O)₃]⁺. The results of labeling condition experiments show that a radiochemical purity higher than 92% can be obtained within 60 min by the reaction of fac-[¹⁸⁸Re (CO)₃]⁺ core in a condition (pH=7.4) with a very small amount (10^-5mol/L) of these three ligands. The stability experiments in vitro demonstrate that fac-[¹⁸⁸Re(CO)₃L¹NH₂]⁺, fac-[¹⁸⁸Re(CO)₃L²H] and fac-[¹⁸⁸Re(CO)₃L³NH₂] do not decompose within 24 h (37 ℃, new born calf serum). Biodistributions results indicate that the complexes with tridentate coordinated ligand systems revealed generally a good and fast clearance from all organs and tissues, primarily through the renalurinary pathway with a small portion retained in the hepatobiliary tract. The predominant route of excretion, the urinary tract, seems to correlate with the lg P values found for the complexes. The highest hepatic retention was found for the complex [¹⁸⁸Re(CO)₃L³NH₂] with a lg P value of －0.36. On the basis of these experiments, it appears that functionalization of biomolecules with tridentatechelating ligand systems is feasible for the labeling with fac-[¹⁸⁸Re(H₂O)₃(CO)₃]⁺.
- ¹⁸⁸Re /
- bifunctional chelating agents /
- biodistributions

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参考文献(11)

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