Transferrin conjugates of triazacyclononane-based bifunctional NE3TA chelates for PET imaging: Synthesis, Cu-64 radiolabeling, and in vitro and in vivo evaluation
Transferrin conjugates of triazacyclononane-based bifunctional NE3TA chelates for PET imaging: Synthesis, Cu-64 radiolabeling, and in vitro and in vivo evaluation
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DOI：
10.1016/j.jinorgbio.2015.10.012
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发表时间：
2016-01-01
影响因子：
3.9
通讯作者：
Chong, Hyun-Soon
中科院分区：
文献类型：
--
作者：
Kang, Chi Soo;Wu, Ningjie;Chong, Hyun-Soon
合成了三种不同的基于聚氨基羧酸酯的双功能NE 3 TA（7-[2-[羧甲基）氨基]乙基]-1，4，7-三氮杂环壬烷-1，4-二乙酸）螯合剂，用于铜64-PET成像应用。使用转铁蛋白（T0）作为结合在许多不同癌细胞中过表达的转铁蛋白受体的模型靶向载体，对双功能螯合物进行比较评估。评价基于NE 3 TA的双功能螯合物的转铁蛋白缀合物缀合物的Cu-64放射性标记。6分别在人血清和前列腺（PC-3）癌细胞中评价了Cu-64-放射性标记偶联物的体外稳定性和细胞摄取。在所测试的三种NE 3 TA-Tf缀合物中，N-NE 3 TA-Tf被鉴定为用Cu-64放射性标记的最佳缀合物J-NE 3 TA-Tf快速结合Cu-64（>98%放射性标记效率，1分钟，RT），并且Cu-64-N-NE 3 TA-Tf在人血清中保持稳定2天，并且在PC-3癌细胞中表现出高摄取。Cu-64-N-NE 3 TA-Tf显示出在24小时内具有快速的血液清除和在PC-3荷瘤小鼠中增加的肿瘤摄取。这种双功能螯合物在温和条件下与Cu-64呈现出高效的螯合化学，其可用于用Cu-64放射性标记各种肿瘤特异性生物分子，用于PET成像应用中的潜在用途。(C)2015 Elsevier Inc. All rights reserved.
Three different polyaminocarboxylate-based bifunctional NE3TA (7-[2-[carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) chelating agents were synthesized for potential use in copper 64-PET imaging applications. The bifunctional chelates were comparatively evaluated using transferrin (TO as a model targeting vector that binds to the transferrin receptor overexpressed in many different cancer cells. The transfertin conjugates conjugates of the NE3TA-based bifunctional chelates were evaluated for radiolabeling with Cu-64. 6 In vitro stability and cellular uptake of Cu-64-radiolabeled conjugates were evaluated in human serum and prostate (PC-3) cancer cells, respectively. Among the three NE3TA-Tf conjugates tested, N-NE3TA-Tf was identified as the best conjugate for radiolabeling with Cu-64.N-NE3TA-Tf rapidly bound to Cu-64 (>98% radiolabeling efficiency, 1 min, RT), and Cu-64-N-NE3TA-Tf remained stable in human serum for 2 days and demonstrated high uptake in PC-3 cancer cells. Cu-64-N-NE3TA-Tf was shown to have rapid blood clearance and increasing tumor uptake in PC-3 tumor bearing mice over a 24 h period. This bifunctional chelate presents highly efficient chelation chemistry with Cu-64 under mild condition that can be applied for radiolabeling of various tumor-specific biomolecules with Cu-64 for potential use in PET imaging applications. (C) 2015 Elsevier Inc. All rights reserved.