Positron emission tomography imaging of tumor angiogenesis with a (61/64)Cu-labeled F(ab')(2) antibody fragment.
Positron emission tomography imaging of tumor angiogenesis with a (61/64)Cu-labeled F(ab')(2) antibody fragment.
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DOI：
10.1021/mp300507r
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发表时间：
2013-02-04
影响因子：
4.9
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Hong H;Zhang Y;Orbay H;Valdovinos HF;Nayak TR;Bean J;Theuer CP;Barnhart TE;Cai W
本研究的目的是表征TRC 105的F（ab '）2片段的体外和体内性质，TRC 105是一种人/鼠嵌合IgG 1单克隆抗体，以高亲合力结合人和鼠CD 105（即内皮糖蛋白），并研究其在61/64 Cu标记后用于肿瘤血管生成的正电子发射断层扫描（PET）成像的潜力。通过胃蛋白酶消化TRC 105得到了高纯度的TRC 105-F（ab '）2，并通过SDS-PAGE、HPLC分析和质谱分析证实了其存在。NOTA-TRC 105-F（ab '）2（NOTA表示1，4，7-三氮杂环壬烷-1，4，7-三乙酸）的61/64 Cu标记以> 75%的产率实现（比活性：~115 GBq/μmol）。PET成像显示在4 T1鼠乳腺癌模型中64 Cu-NOTA TRC 105-F（ab '）2的快速肿瘤摄取（在注射后0.5、3、16、24和48小时分别为5.8 ± 0.8、7.6 ± 0.6、5.6 ± 0.4、5.0 ± 0.6和3.8 ± 0.7%ID/g; n = 4）。由于肿瘤摄取在注射后3小时达到峰值，因此61 Cu-NOTA-TRC 105-F（ab '）2在注射后3和8小时也给出了良好的肿瘤对比度。通过阻断研究和组织病理学证实了示踪剂的CD 105特异性。总之，使用F（ab '）2片段导致比放射性标记的完整抗体（其通常在注射后24小时后达到峰值）更快的肿瘤摄取（其在注射后3小时达到峰值），这可以允许在未来的临床研究中进行当天免疫PET成像。
The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')2 fragment of TRC105, a human/murine chimeric IgG1 monoclonal antibody that binds with high avidity to human and murine CD105 (i.e. endoglin), and investigate its potential for positron emission tomography (PET) imaging of tumor angiogenesis after 61/64Cu-labeling. TRC105-F(ab')2 of high purity was produced by pepsin digestion of TRC105, which was confirmed by SDS-PAGE, HPLC analysis, and mass spectrometry. 61/64Cu-labeling of NOTA-TRC105-F(ab')2 (NOTA denotes 1,4,7-triazacyclononane-1,4,7-triacetic acid) was achieved with yields of > 75% (specific activity: ~115 GBq/μmol). PET imaging revealed rapid tumor uptake of 64Cu-NOTA TRC105-F(ab')2 in the 4T1 murine breast cancer model (5.8 ± 0.8, 7.6 ± 0.6, 5.6 ± 0.4, 5.0 ± 0.6, and 3.8 ± 0.7 %ID/g at 0.5, 3, 16, 24, and 48 h post-injection respectively; n = 4). Since tumor uptake peaked at 3 h post-injection, 61Cu-NOTA-TRC105-F(ab')2 also gave good tumor contrast at 3 and 8 h post-injection. CD105 specificity of the tracers was confirmed by blocking studies and histopathology. In conclusion, the use of a F(ab')2 fragment led to more rapid tumor uptake (which peaked at 3 h post-injection) than radiolabeled intact antibody (which often peaked after 24 h post-injection), which may allow for same day immunoPET imaging in future clinical studies.
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影响因子：
9.3
作者：
Dijkers, Eli C. F.;Kosterink, Jos G. W.;Lub-de Hooge, Marjolijn N.
通讯作者：
Lub-de Hooge, Marjolijn N.
DOI：
10.1007/s00259-007-0503-5
发表时间：
2007-12-01
影响因子：
9.1
作者：
Cai, Weibo;Ebrahimnejad, Alireza;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
DOI：
10.1007/s00259-011-1930-x
发表时间：
2012-01
影响因子：
9.1
作者：
Hong H;Severin GW;Yang Y;Engle JW;Zhang Y;Barnhart TE;Liu G;Leigh BR;Nickles RJ;Cai W
通讯作者：
Cai W
影响因子：
82.9
作者：
Backer, Marina V.;Levashova, Zoya;Backer, Joseph M.
通讯作者：
Backer, Joseph M.
影响因子：
11.2
作者：
Cai, Weibo;Wu, Yun;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan