铼[^(188)Re]羰基化合物标记新双功能螯合剂的研究  

Research of novel bifunctional chelating agents for the ^(188)Re-tricarbonyl complexes labeling

作　　者：夏姣云[1] 汪勇先[1] 李世强[1] 于俊峰[1] 唐林[1] 尹端沚[1] 

机构地区：[1]中国科学院上海应用物理研究所放射性药物研究中心

出　　处：《核技术》2006年第12期921-926,共6页Nuclear Techniques

基　　金：中国科学院知识创新工程重大项目(KJCXI-SW-08);中国科学院创新工程领域前沿项目(55200321)资助;所导向项目"核技术病毒检测及同位素标记";国家自然科学基金(10405034)资助

摘　　要：合成了三种新的三齿配体L1NH2、L2H和L3NH2,用于设计合成新的以fac-[188Re(CO)3]+为核心的放射性药物。标记条件实验证明,三种配体在低浓度(10-5mol/L)的条件下,反应时间为60min内,配体标记率可达88%以上,放射化学纯度大于90%。同时合成了冷羰基铼配合物fac-[Re(CO)3L1NH2]+、fac-[Re(CO)3L2H]和fac-[Re(CO)3L3NH2]作为参照标准品。稳定性实验也说明三种标记物均具有很高的体外稳定性,标记后24h内基本不发生分解;组氨酸和半胱氨酸体外竞争实验证实fac-[188Re(CO)3L1NH2]+和fac-[188Re(CO)3L2H]比fac-[188Re(CO)3L3NH2]稳定,不易被组氨酸和半胱氨酸取代,可能羧基上的-OH与fac-[188Re(CO)3]+的配位能力比吡啶环上的N稍低,也可说明三种配体均是较理想的标记fac-[188Re(CO)3(H2O)3]+的双功能螯合剂。The organometallic precursor fac-[^188Re （CO）3（H2O）3]^＋ is reacted with three novel tridentate ligands （L^1NH2, L^2H, L^3NH2） and the properties of their ^188Re complexes in vivo have been evaluated. The results of labeling condition experiments show that a radiochemical purity higher than 90% can be obtained within 60 min by the reaction of fac-[^188Re （CO）3]^＋ core in the condition of pH=7.4 with a very small amount （10^-5 mol/L） of these three new ligands. At the same time, three Re-tricarbonyl complexes of three ligands were also synthesized as reference samples, which were used to confirm the structures of ^188Re-tricarbonyl complexes of three ligands by HPLC. The stability experiments in vitro demonstrate that fac-[^188Re（CO）3L^1NH2]^＋, fac-[^188Re（CO）3L^2H] and fac-[^188Re（CO）3L^3NH2] do not decompose within 24 h （37 ℃, in new born small calf serum）. Histidine and cysteine challenge experiments （37℃, PBS, pH=7.4） show that fac-[^188Re（CO）3L^1NH2]^＋ and fac-[^188Re（CO）3L^2H] have higher stabilities than fac-[^188Re（CO）3L^3NH2], which indicates that the combination ability of -OH in -COOH with fac-[^188Re（CO）3L^2H] core was higher than that of-N in pyridine. It is also indicated that three novel tridentate ligands （L^1NH2, L^2H, L^3NH2） are better bifunctional chelating agents for the labeling by the precursor fac-[^188Re （CO）3（H2O）3]^＋.

关 键 词：铼-188 羰基化合物 双功能螯合剂 

分 类 号：R811.5[医药卫生—放射医学]