Positron emission tomography imaging of tumor angiogenesis with a 66Ga-labeled monoclonal antibody.
Positron emission tomography imaging of tumor angiogenesis with a 66Ga-labeled monoclonal antibody.
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DOI：
10.1021/mp300019c
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发表时间：
2012-05-07
影响因子：
4.9
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Engle JW;Hong H;Zhang Y;Valdovinos HF;Myklejord DV;Barnhart TE;Theuer CP;Nickles RJ;Cai W
本研究的目的是开发一种基于66 Ga的正电子发射断层扫描（PET）示踪剂，用于肿瘤血管生成（癌症的标志）过程中CD 105表达的非侵入性成像。使用回旋加速器用natZn或同位素富集的66 Zn靶产生66 Ga。将嵌合抗CD 105单克隆抗体TRC 105与2-S-（4-异硫氰酸基苄基）-1，4，7-三氮杂环壬烷-1，4，7-三乙酸（p-SCN-Bn-NOTA）偶联，用66 Ga标记。基于流式细胞术分析，在TRC 105和N 0 TATRC 105之间未观察到CD 105结合亲和力或特异性的差异。校正到轰击结束时，两种靶富集的66 Ga对NOTA的反应性在74和222 GBq/μmol之间，< 2 ppb of cold gallium. 66Ga-labeling was achieved with >放射化学产率为80%。连续PET成像显示，66 Ga-NOTA-TRC 105的鼠乳腺癌4 T1肿瘤摄取在注射后4、20和36小时分别为5.9 ± 1.6、8.5 ± 0.6和9.0 ± 0.6%ID/g（n = 4）。在最后一个时间点，肿瘤摄取高于所有器官，这提供了极好的肿瘤对比度，肿瘤/肌肉比为10.1 ± 1.1。通过伽马计数测量的生物分布数据与PET结果一致。阻断实验、用66 Ga-NOTA-西妥昔单抗的对照研究以及离体组织学都证实了66 Ga-NOTA-TRC 105的体内靶特异性。以高比活度66 Ga（> 700 GBq/μmol）作为放射性标记的成功PET成像为未来使用抗体或其他靶向配体的PET研究开辟了许多新的可能性。
The goal of this study was to develop a 66Ga-based positron emission tomography (PET) tracer for non-invasive imaging of CD105 expression during tumor angiogenesis, a hallmark of cancer. 66Ga was produced using a cyclotron with natZn or isotopically enriched 66Zn targets. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (p-SCN-Bn-NOTA) and labeled with 66Ga. No difference in CD105 binding affinity or specificity was observed between TRC105 and NOTATRC105 based on flow cytometry analysis. Reactivity of 66Ga for NOTA, corrected to the end of bombardment, was between 74 and 222 GBq/μmol for both target enrichments with < 2 ppb of cold gallium. 66Ga-labeling was achieved with > 80% radiochemical yield. Serial PET imaging revealed that the murine breast cancer 4T1 tumor uptake of 66Ga-NOTA-TRC105 was 5.9 ± 1.6, 8.5 ± 0.6, and 9.0 ± 0.6 %ID/g at 4, 20, and 36 h post-injection, respectively (n = 4). At the last time point, tumor uptake was higher than all organs which gave excellent tumor contrast with a tumor/muscle ratio of 10.1 ± 1.1. Biodistribution data as measured by gamma counting were consistent with the PET findings. Blocking experiment, control studies with 66Ga-NOTA-cetuximab, as well as ex vivo histology all confirmed the in vivo target specificity of 66Ga-NOTA-TRC105. Successful PET imaging with high specific activity 66Ga (> 700 GBq/μmol has been achieved) as the radiolabel opens many new possibilities for future PET research with antibodies or other targeting ligands.
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影响因子：
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影响因子：
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