New Bifunctional Chelator for 64Cu-Immuno-Positron Emission Tomography
New Bifunctional Chelator for 64Cu-Immuno-Positron Emission Tomography
复制标题
DOI：
10.1021/bc400192a
复制
发表时间：
2013-08-01
影响因子：
4.7
通讯作者：
Yoo, Jeongsoo
中科院分区：
文献类型：
--
作者：
Pandya, Darpan N.;Bhatt, Nikunj;Yoo, Jeongsoo
以环拉胺为原料，以较高的总收率合成了一种新的四氮杂大环双功能螯合剂TE 2A-Bn-NCS。在TE 2A的N-原子上引入额外的官能团（NCS），用于与抗体的特异性缀合。TE 2A-Bn-NCS的Cu配合物在酸解络合和循环伏安研究中显示出高的动力学稳定性。Cu-TE_2A-Bn-NH_2配合物的X-射线结构测定证实了其八面体构型，其中铜原子与赤道位置的四个大环氮原子强配位，两个羧酸氧原子占据拉长的轴向位置。将曲妥珠单抗与TE 2A-Bn-NCS偶联，然后在室温下10 min内用Cu-64进行放射性标记。生物分布研究表明，Cu-64标记的TE 2A-Bn-NCS-曲妥珠单抗偶联物在生理条件下保持高稳定性，并且在动物模型中通过Cu-64-免疫正电子发射断层扫描成像可清晰地观察NIH 3T6.7肿瘤长达3天。
A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic vokammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with Cu-64 at room temperature within 10 min. Biodistribution studies showed that the Cu-64-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were dearly visualized up to 3 days by Cu-64-inununo-positron emission tomography imaging in animal models.