期刊
ANGIOGENESIS
卷 16, 期 3, 页码 663-674出版社
SPRINGER
DOI: 10.1007/s10456-013-9344-y
关键词
Breast cancer; Tumor angiogenesis; Lung metastasis; Positron emission tomography (PET); Near-infrared fluorescence (NIRF); CD105/endoglin; ImmunoPET; Image-guided surgery
资金
- University of Wisconsin Carbone Cancer Center
- Department of Defense [W81XWH-11-1-0644]
- Elsa U. Pardee Foundation
The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and Cu-64 to yield Cu-64-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of Cu-64-NOTA-TRC105-800CW was 11.9 +/- A 1.2, 13.9 +/- A 3.9, and 13.4 +/- A 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with Cu-64-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of Cu-64-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据