Comparative Assessment of Complex Stabilities of Radiocopper Chelating Agents by a Combination of Complex Challenge and in vivo Experiments
Comparative Assessment of Complex Stabilities of Radiocopper Chelating Agents by a Combination of Complex Challenge and in vivo Experiments
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DOI：
10.1002/cmdc.201500132
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发表时间：
2015-07-01
期刊：
影响因子：
3.4
通讯作者：
Waengler, Carmen
中科院分区：
文献类型：
--
作者：
Litau, Shanna;Seibold, Uwe;Waengler, Carmen
对于用作体内正电子发射断层扫描（PET）成像剂的生物分子的Cu-64放射性标记，通常应用各种螯合剂。目前还没有确定哪种最有效的螯合剂NODA-GA（（1，4，7-三氮杂环壬烷-4，7-二基）二乙酸-1-谷氨酸），CB-TE 2A（2，2-（1，4，8，11-四氮杂双环[6.6.2]十六烷-4，11-二基）二乙酸）或CB-TE 1A-GA（1，4，8，11-四氮杂双环[6.6.2]十六烷-4，11-二基-8-乙酸-1-戊二酸）形成最稳定的络合物，从而产生最高质量的PET图像。我们通过复合物挑战和体内方法的组合确定了这三种螯合剂的Cu-64复合物稳定性。为此，合成了具有胃泌素释放肽受体（GRPR）-亲和肽PESIN和整合素（v3）-亲和C（RGDfC）四聚体的螯合剂的生物缀合物，并以优异的产率和比活性用Cu-64放射性标记。Cu-64标记的生物分子通过用相应的其他螯合剂作为挑战者进行挑战实验来评价它们的体外复合物稳定性。还测定了复合物的体内稳定性，表明Cu-64-CB-TE 1A-GA复合物在两种实验设置中的稳定性最高。因此，CB-TE 1A-GA是 * Cu标记的放射性示踪剂和体内成像应用的最合适的螯合剂。
For Cu-64 radiolabeling of biomolecules to be used as in vivo positron emission tomography (PET) imaging agents, various chelators are commonly applied. It has not yet been determined which of the most potent chelatorsNODA-GA ((1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid), CB-TE2A (2,2-(1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl)diacetic acid), or CB-TE1A-GA (1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl-8-acetic acid-1-glutaric acid)forms the most stable complexes resulting in PET images of highest quality. We determined the Cu-64 complex stabilities for these three chelators by a combination of complex challenge and an in vivo approach. For this purpose, bioconjugates of the chelating agents with the gastrin-releasing peptide receptor (GRPR)-affine peptide PESIN and an integrin(v3)-affine c(RGDfC) tetramer were synthesized and radiolabeled with Cu-64 in excellent yields and specific activities. The Cu-64-labeled biomolecules were evaluated for their complex stabilities in vitro by conducting a challenge experiment with the respective other chelators as challengers. The in vivo stabilities of the complexes were also determined, showing the highest stability for the Cu-64-CB-TE1A-GA complex in both experimental setups. Therefore, CB-TE1A-GA is the most appropriate chelating agent for *Cu-labeled radiotracers and in vivo imaging applications.