Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro
Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro
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DOI：
10.1007/s002590050283
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发表时间：
1998-07-01
期刊：
影响因子：
--
通讯作者：
Blower, PJ
中科院分区：
文献类型：
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作者：
Dearling, JLJ;Lewis, JS;Blower, PJ
众所周知，以Cu-62或Cu-64标记的灌注示踪剂CuPTSM被认为通过生物还原机制非选择性地困在细胞中。有人提出，通过修饰配体以增加其电子供体强度（例如通过添加烷基官能团或用氧配体取代硫配体），铜配合物将变得不那么容易还原，从而可以开发出对缺氧组织具有选择性的示踪剂。本研究的目的是基于双（硫代氨基脲）（13个配体）和双（水杨醛二胺）（3个配体）骨架制备两种系列的cu -64标记配合物，并评估它们在细胞中摄取的缺氧依赖性。将这些复合物与中国仓鼠卵巢细胞在常氧和低氧条件下孵育，离心分离细胞，测定90 min内不同时间点的放射性摄取。两个系列的几个成员都表现出显著的(P
The well-known perfusion tracer CuPTSM, labelled with Cu-62 or Cu-64 is believed to be trapped in cells non-selectively by a bioreductive mechanism. It is proposed that by modifying the ligand to increase its electron donor strength (for example by adding alkyl functionality or replacing sulphur ligands with oxygen ligands), the copper complexes will become less easily reduced and tracers with selectivity for hypoxic tissues could thus be developed. The aim of this work was to prepare Cu-64-labelled complexes of two series of ligands, based on the bis(thiosemicarbazone) (13 ligands) and bis(salicylaldimine) (3 ligands) skeletons, and to evaluate the hypoxia dependence of their uptake in cells. The complexes were incubated with Chinese hamster ovary cells under normoxic and hypoxic conditions, and the cells isolated by centrifugation to determine radioactivity uptake at various time points up to 90 min. Several members of both series demonstrated significant (P