Click-chemistry strategy for labeling antibodies with copper-64 via a cross-bridged tetraazamacrocyclic chelator scaffold.
Click-chemistry strategy for labeling antibodies with copper-64 via a cross-bridged tetraazamacrocyclic chelator scaffold.
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DOI：
10.1021/acs.bioconjchem.5b00102
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发表时间：
2015-04-15
影响因子：
4.7
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Kumar A;Hao G;Liu L;Ramezani S;Hsieh JT;Öz OK;Sun X
我们报告了一种基于点击化学的64 Cu标记抗体的模块化策略（t1/2 = 12.7 h; β+ 0.656 MeV，17.4%; β− 0.573 MeV，39%; EC 43%），使用交联的四氮杂大环（CB-TE 2A）类似物，否则需要苛刻的条件，这使得CB-TE 2A类似物不能充分用于蛋白质标记，尽管事实上它们形成具有高体内稳定性的动力学惰性铜络合物。我们的策略包括用64 Cu预标记基于CB-TE 2A的支架（CB-TE 2A-1C），以及其随后通过四嗪-双烯介导的点击化学与抗体反应。通过标记两种单克隆抗体，抗PSMA抗体（YPSMA-1）和嵌合抗磷脂酰丝氨酸抗体（Bavituximab），证明了该策略的有效性。抗体的免疫反应性在四嗪修饰和点击化学64 Cu标记后保持不变。为了进一步证明模块化64 Cu标记策略的实用性，我们在小鼠异种移植模型中测试了用64 Cu标记的bavituximab进行的肿瘤正电子发射断层扫描（PET）成像。肿瘤可视化和标记抗体的摄取显示了点击化学策略的多功能性。
We report a click-chemistry based modular strategy for antibody labeling with 64Cu (t1/2 = 12.7 h; β+ 0.656 MeV, 17.4%; β− 0.573 MeV, 39%; EC 43%) under ambient condition utilizing a cross-bridged tetraazamacrocyclic (CB-TE2A) analogue, which otherwise requires harsh conditions that make the CB-TE2A analogues underutilized for protein labeling despite the fact that they form kinetically inert copper complexes with high in vivo stability. Our strategy involves prelabeling a CB-TE2A based scaffold (CB-TE2A-1C) with 64Cu and its subsequent reaction with an antibody via the tetrazine-norbornene mediated click chemistry. The effectiveness of this strategy was demonstrated by labeling two monoclonal antibodies, an anti-PSMA antibody (YPSMA-1) and a chimeric anti-phosphatidylserine antibody (Bavituximab). The immunoreactivity of the antibodies remained unchanged after the tetrazine modification and click-chemistry 64Cu labeling. To further demonstrate the practicality of the modular 64Cu labeling strategy, we tested positron emission tomography (PET) imaging of tumor with the 64Cu-labeled bavituximab in a mouse xenograft model. The tumor visualization and uptake of the labeled antibody exhibited the versatility of the click-chemistry strategy.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
影响因子：
16.6
作者：
Devaraj, Neal K.;Upadhyay, Rabi;Hatin, Jered B.;Hilderbrand, Scott A.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
3.1
作者：
Dearling JL;Voss SD;Dunning P;Snay E;Fahey F;Smith SV;Huston JS;Meares CF;Treves ST;Packard AB
通讯作者：
Packard AB
DOI：
10.1007/s00259-009-1158-1
发表时间：
2009-09
影响因子：
9.1
作者：
Niu, Gang;Li, Zibo;Cao, Qizhen;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
3.1
作者：
Chen, XY;Liu, S;Conti, PS
通讯作者：
Conti, PS