Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS
Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS
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DOI：
10.1016/j.nucmedbio.2004.09.004
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Anderson, CJ
中科院分区：
文献类型：
--
作者：
Boswell, CA;McQuade, P;Anderson, CJ
交叉桥联的四胺配体4，11-bis(carboxymethyl)-1，4，8，11-tetraazabicyclo[6.6.2]hexadecane(H_2CB-TE_(2a))可以形成比相应的非交桥类似物1，4，8，11-tetraazacyclotetradecane-1，4，8，11-tetraacetic酸(TETA)更稳定的放射性-铜配合物。CB-TE2A的铜-NaT(II)络合物的结构以前已通过X射线结晶学确定；然而，由于无法在放射性示踪剂水平上通过紫外吸收检测到该络合物，因此无法直接用高压液相色谱对相应的铜-络合物进行表征。建立了一系列铜-NaT(II)-四氮杂大环化合物的反相高效液相色谱分离方法，用于表征和评价相应的无载体的铜-标记的配合物的纯度。将该方法与质谱仪联用，也实现了铜-标记化合物的鉴定。进一步将放射-液-质联用技术应用于铜--氮杂大环化合物体内代谢产物的研究。(C)2005 Elsevier Inc.保留所有权利。
The cross-bridged tetraamine ligand 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A) allows formation of a radio-copper complex with higher in vivo stability than that of the corresponding non-cross-bridged analog 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). The structure of the Cu-nat(II) complex of CB-TE2A has been previously determined by X-ray crystallography; however, direct high-pressure liquid chromatography (HPLC) characterization of the corresponding Cu-64 complex was inaccessible due to the inability to detect the complex by ultraviolet absorbance at the radiotracer level. A reverse-phase HPLC separation of a series of Cu-nat(II)-tetraazamacrocyclic complexes, both traditional and cross-bridged, was developed and applied toward characterization and assessment of the purity of the corresponding no-carrier-added Cu-64-labeled complexes. Verification of the identity of copper-64-labeled compounds was also achieved by coupling this HPLC method with mass spectrometry. The radio-liquid chromatography/mass spectrometry methodology was further extended to study the in vivo metabolic fates of Cu-64-azarnacrocyclic complexes. (C) 2005 Elsevier Inc. All rights reserved.