Comparison of conjugation strategies of cross-bridged macrocyclic chelators with cetuximab for copper-64 radiolabeling and PET imaging of EGFR in colorectal tumor-bearing mice.
Comparison of conjugation strategies of cross-bridged macrocyclic chelators with cetuximab for copper-64 radiolabeling and PET imaging of EGFR in colorectal tumor-bearing mice.
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DOI：
10.1021/mp500004m
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发表时间：
2014-11-03
影响因子：
4.9
通讯作者：
Anderson CJ
中科院分区：
文献类型：
--
作者：
Zeng D;Guo Y;White AG;Cai Z;Modi J;Ferdani R;Anderson CJ
表皮生长因子受体（EGFR）在多种实体瘤中过表达，并已成为癌症成像和治疗的良好特征靶点。西妥昔单抗是FDA批准的第一个靶向EGFR的mAb，用于治疗转移性结直肠癌和头颈癌。先前的研究表明，64 Cu（T1/2 = 12.7 h; β+（17.4%））标记的DOTA-西妥昔单抗显示出EGFR阳性肿瘤的PET成像的前景;然而，该化合物的体内稳定性受到质疑。在这项研究中，两个最近开发的交联大环螯合剂（CB-TE 1A 1 P和CB-TE 1 K1 P）使用标准NHS偶联程序和/或应变促进叠氮化物-炔环加成（SPAAC）方法与西妥昔单抗偶联。比较了所得西妥昔单抗偶联物的放射性标记和体外/体内评价。用CB-TE 1 K1 P-PEG 4-点击-西妥昔单抗缀合物获得了改善的Cu-64标记效率和高比活性（684 kBq/μg，衰减校正至轰击结束）。饱和结合测定表明，制备的西妥昔单抗缀合物在HCT 116人结肠直肠肿瘤细胞膜中具有相当的亲和力（1.32-2.00 nM）。在随后的体内评价中，64 Cu-CB-TE 1 K1 P-PEG 4-click-cetuximab显示出比其他64 Cu标记的西妥昔单抗缀合物更快的肾清除率和更高的肿瘤/非肿瘤比率，并且它显示出EGFR阳性肿瘤的成像和治疗的最大前景。
Epidermal growth-factor receptor (EGFR) is overexpressed in a wide variety of solid tumors and has served as a well-characterized target for cancer imaging and therapy. Cetuximab was the first mAb targeting EGFR approved by the FDA for the treatment of metastatic colorectal and head and neck cancers. Previous studies showed that 64Cu (T1/2 = 12.7 h; β+ (17.4%)) labeled DOTA–cetuximab showed promise for PET imaging of EGFR-positive tumors; however the in vivo stability of this compound has been questioned. In this study, two recently developed cross-bridged macrocyclic chelators (CB-TE1A1P and CB-TE1K1P) were conjugated to cetuximab using standard NHS coupling procedures and/or strain-promoted azide–alkyne cycloaddition (SPAAC) methodologies. The radiolabeling and in vitro/vivo evaluation of the resulting cetuximab conjugates were compared. Improved Cu-64 labeling efficiency and high specific activity (684 kBq/μg, decay corrected to the end of bombardment) were obtained with the CB-TE1K1P-PEG4-click-cetuximab conjugate. Saturation binding assays indicated that the prepared cetuximab conjugates had comparable affinity (1.32–2.00 nM) in the HCT116 human colorectal tumor cell membranes. In the subsequent in vivo evaluation, 64Cu-CB-TE1K1P-PEG4-click-cetuximab demonstrated more rapid renal clearance with a higher tumor/nontumor ratio than other 64Cu-labeled cetuximab conjugates, and it shows the greatest promise for imaging and therapy of EGFR-positive tumors.
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DOI：
10.1039/c1dt11743b
发表时间：
2012-02-21
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Ferdani R;Stigers DJ;Fiamengo AL;Wei L;Li BT;Golen JA;Rheingold AL;Weisman GR;Wong EH;Anderson CJ
通讯作者：
Anderson CJ
影响因子：
6.7
作者：
Mucha, A.;Kunert, A.;Kafarski, P.
通讯作者：
Kafarski, P.
影响因子：
3.4
作者：
Li, Wen Ping;Meyer, Laura A.;Anderson, Carolyn J.
通讯作者：
Anderson, Carolyn J.
影响因子：
158.5
作者：
Jonker, Derek J.;O'Callaghan, Chris J.;Moore, Malcolm J.
通讯作者：
Moore, Malcolm J.
DOI：
10.1007/s00259-006-0361-6
发表时间：
2007-06-01
影响因子：
9.1
作者：
Cai, Weibo;Chen, Kai;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan