Promising bifunctional chelators for copper 64-PET imaging: practical (64)Cu radiolabeling and high in vitro and in vivo complex stability.
Promising bifunctional chelators for copper 64-PET imaging: practical (64)Cu radiolabeling and high in vitro and in vivo complex stability.
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DOI：
10.1007/s00775-015-1318-7
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发表时间：
2016-04
影响因子：
3
通讯作者：
Chong, Hyun-Soon
中科院分区：
文献类型：
--
作者：
Wu, Ningjie;Kang, Chi Soo;Sin, Inseok;Ren, Siyuan;Liu, Dijie;Ruthengael, Varyanna C.;Lewis, Michael R.;Chong, Hyun-Soon
采用铜-的正电子发射断层扫描是一种敏感的、无创的肿瘤诊断和分期的成像技术。双官能络合剂具有快速的放射性标记动力学和与64Cu高的络合物稳定性，是靶向PET成像的关键组成部分。研究了3p-C-NE3TA、3p-C-NOTA和3p-C-DE4TA三种双功能络合物与~(64)Cu在体内外的络合动力学和稳定性。六齿3P-C-NOTA和七齿3P-C-NE3TA具有较小的TACN基大环骨架，而非齿3P-C-DE4TA则构筑在较大的环上。对常用的64Cu、八齿C-DOTA和六齿C-NOTA的络合物也进行了比较评价。在温和的条件下，研究了~(64)Cu双功能络合剂的放射性标记动力学。所有双功能螯合物在室温下都能立即与64Cu结合，具有出色的放射性标记效率。C-DOTA对64铜的结合效率低于所有其他络合物。所有的~(64)Cu标记的双功能络合物在人血清中都保持稳定，两天内~(64)Cu没有任何损失。在过量EDTA的作用下，3p-C-NE3TA和3p-C-NOTA的64Cu络合物比64Cu-C-DOTA和64Cu-C-DE4TA更稳定。3P-C-NE3TA和3P-C-NOTA在体内外的稳定性与64Cu-C-NOTA相当。体内分布结果表明，~(64)Cu标记的3P-C-NOTA和3P-C-NE3TA具有良好的体内络合物稳定性，而~(64)Cu-3P-C-DE4TA在小鼠体内有较高的肾脏和肝脏滞留率。体外和体内研究结果表明，3P-C-NOTA和3P-C-NE3TA与~(64)Cu具有良好的络合化学性能，具有潜在的PET成像应用前景。
Positron emission tomography (PET) using copper-64 is a sensitive and non-invasive imaging technique for diagnosis and staging of cancer. A bifunctional chelator that can present rapid radiolabeling kinetics and high complex stability with 64Cu is a critical component for targeted PET imaging. Bifunctional chelates 3p-C-NE3TA, 3p-C-NOTA, and 3p-C-DE4TA were evaluated for complexation kinetics and stability with 64Cu in vitro and in vivo. Hexadentate 3p-C-NOTA and heptadentate 3p-C-NE3TA possess a smaller TACN-based macrocyclic backbone, while nonadentate 3p-C-DE4TA is constructed on a larger CYCLEN-based ring. The frequently explored chelates of 64Cu, octadentate C-DOTA and hexadentate C-NOTA were also comparatively evaluated. Radiolabeling kinetics of bifunctional chelators with 64Cu was assessed under mild conditions. All bifunctional chelates instantly bound to 64Cu in excellent radiolabeling efficiency at room temperature. C-DOTA was less efficient in binding 64Cu than all other chelates. All 64Cu-radiolabeled bifunctional chelates remained stable in human serum without any loss of 64Cu for 2 days. When challenged by an excess amount of EDTA, 64Cu complexes of 3p-C-NE3TA and 3p-C-NOTA were shown to be more stable than 64Cu-C-DOTA and 64Cu-C-DE4TA. 3p-C-NE3TA and 3p-C-NOTA displayed comparable in vitro and in vivo complex stability to 64Cu-C-NOTA. In vivo biodistribution result indicates that the 64Cu-radiolabeled complexes of 3p-C-NOTA and 3p-C-NE3TA possess excellent in vivo complex stability, while 64Cu-3p-C-DE4TA was dissociated as evidenced by high renal and liver retention in mice. The results of in vitro and in vivo studies suggest that the bifunctional chelates 3p-C-NOTA and 3p-C-NE3TA offer excellent chelation chemistry with 64Cu for potential PET imaging applications.
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影响因子：
3.9
作者：
Kang, Chi Soo;Wu, Ningjie;Chong, Hyun-Soon
通讯作者：
Chong, Hyun-Soon
影响因子：
4.7
作者：
Pandya, Darpan N.;Bhatt, Nikunj;Yoo, Jeongsoo
通讯作者：
Yoo, Jeongsoo
影响因子：
3.1
作者：
De Silva, Ravindra A.;Jain, Sandeep;Rogers, Buck E.
通讯作者：
Rogers, Buck E.
影响因子：
2.7
作者：
Chong, Hyun-Soon;Mhaske, Santosh;Sun, Xiankai
通讯作者：
Sun, Xiankai
影响因子：
18.3
作者：
Shokeen M;Anderson CJ
通讯作者：
Anderson CJ