Positron Emission Tomography Imaging of Tumor Angiogenesis with a 66Ga-Labeled Monoclonal Antibody

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• 作者：Jonathan W. Engle ; Hao Hong ; Yin Zhang ; Hector F. Valdovinos ; Duane V. Myklejord ; Todd E. Barnhart ; Charles P. Theuer ; Robert J. Nickles ; Weibo Cai
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：May 7, 2012
• 年：2012
• 卷：9
• 期：5
• 页码：1441-1448
• 全文大小：417K
• 年卷期：v.9,no.5(May 7, 2012)
• ISSN：1543-8392

文摘

The goal of this study was to develop a ⁶⁶Ga-based positron emission tomography (PET) tracer for noninvasive 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 NOTA-TRC105 based on flow cytometry analysis. Reactivity of ⁶⁶Ga for NOTA, corrected to the end of bombardment, was between 74 and 222 GBq/渭mol 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 卤 1.6, 8.5 卤 0.6, and 9.0 卤 0.6% ID/g at 4, 20, and 36 h postinjection, respectively (n = 4). At the last time point, tumor uptake was higher than that of all organs, which gave excellent tumor contrast with a tumor/muscle ratio of 10.1 卤 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/渭mol has been achieved) as the radiolabel opens many new possibilities for future PET research with antibodies or other targeting ligands.

Keywords:

⁶⁶Ga; positron emission tomography (PET); tumor angiogenesis; CD105/endoglin; TRC105; breast cancer