Improved in vivo stability of actinium-225 macrocyclic complexes
Improved in vivo stability of actinium-225 macrocyclic complexes
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DOI：
10.1021/jm990141f
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发表时间：
1999-07-29
影响因子：
7.3
通讯作者：
Brechbiel, MW
中科院分区：
文献类型：
--
作者：
Deal, KA;Davis, IA;Brechbiel, MW
锕-225（Ac-225）的有利核特性导致了这种同位素用于放射免疫治疗的建议。为了降低游离Ac-225的毒性，评价了一系列配体的体内稳定性。Ac-225从无环螯合剂中的损失导致高肝脏摄取和差的全身清除。评价了大环配体c-DOTA、PEPA和HEHA，Ac-225-HEHA在体内显示出优异的稳定性。与EDTA、DTPA、DOTA或PEPA螯合的Ac-225允许放射性核素在肝脏中大量蓄积，而Ac-225-HEHA复合物基本上在给药后几分钟内排泄。将讨论配体和放射性标记的复合物的制备和生物分布结果。
The favorable nuclear properties of actinium-225 (Ac-225) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free Ac-225, a series of ligands were evaluated for stability in vivo. Loss of Ac-225 from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and Ac-225-HEHA showed exceptional stability in vivo. Ac-225 chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the Liver, while the Ac-225-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.