铼羰基化合物的制备及其在小鼠体内的生物分布

选择三齿配基L₁，L₂，L₃及L₄（L₁ =组氨酸, L₂ =次氮基三乙酸，L₃= 2-吡啶甲基胺 N, N-二乙酸，L₄ =二（2-吡啶甲基）-胺）作为双功能螯合剂可以连接受体、多肽、蛋白等靶向分子，用于设计合成新的以[¹⁸⁸Re(CO)₃]⁺为核心的放射性药物。标记实验表明，4个配基的浓度在1×10^-5～1×10^-4mol/L，反应时间为30min时，放射化学产率大于90％，用HPLC分离后，放射化学纯度大于95％。电泳实验表明，配合物显示不同的价态。稳定性实验表明，4种配合物在体外稳定，24h几乎不发生分解。组氨酸与半胱氨酸竞争实验说明，24h内4个配合物很难发生配基与半胱氨酸的交换反应，而在组氨酸溶液中，除L₂形成的配合物相对来说不稳定外，其它3个较稳定。是否在体内有很高的稳定性，还需实验进一步证实。小鼠动物试验表明，4个配合物均能较快地从血液和多数组织器官中清除，主要在肝和肾中浓集，是较理想的双功能螯合剂。

Synthesis and Biodistribution of 188Re-Tricarbonyl Complexes

Radiolabeling of biologically active molecules with the fac [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ unit has been of primary interest in recent years. Therefore, the tridentate ligands L₁~L₄ (L₁ =histidine, L₂ = nitrilotriacetic, L₃ = 2-picolylamine-N,N- diacetic acid, L₄ = bis(2-pyridymethy)amine)were evaluated in radiochemical reactions with the fac[¹⁸⁸Re(CO)₃(H₂O)₃]⁺. These reactions yielded the radioactive building blocks fac[¹⁸⁸Re(CO)₃L] (L = L₁~L₄), which were identified by HPLC. Tricarbonyl complexes, with lg P values ranging from -2.23 to 2.18, were obtained in yields higher than 90% using ligand concentrations within the 1×10^-5~1×10^-4 mol/L range. Competition studies with cysteine and histidine revealed high stability for all of these radioactive complexes, and biodistribution studies in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion occurring primarily through the renal urinary pathway. In summary, complexes (L₁~L₄) are potent chelators for the future functionalization of biomolecules.