ImmunoPET of CD146 in Orthotopic and Metastatic Breast Cancer Models

体内分布 转移性乳腺癌 乳腺癌 CD146号 染色 病理 流式细胞术 H&E染色 转移 免疫组织化学 癌症 化学 离体 单克隆抗体 医学 显像剂 内科学 癌症研究 血管生成 体内 肿瘤科 抗体 免疫学 生物 川地34 体外 生物化学 遗传学 干细胞 生物技术
作者
Cuicui Li,Lei Kang,Kevin Fan,Carolina A. Ferreira,Kaelyn V Becker,Nan Huo,Hanxiao Liu,Yunan Yang,Jonathan W. Engle,Rongfu Wang,Xiaojie Xu,Dawei Jiang,Weibo Cai
出处
期刊:Bioconjugate Chemistry [American Chemical Society]
卷期号:32 (7): 1306-1314 被引量:3
标识
DOI:10.1021/acs.bioconjchem.0c00649
摘要

The overexpression of CD146 in breast cancer is considered a hallmark of tumor progression and metastasis, particularly in triple negative breast cancer. Aimed at imaging differential CD146 expressions in breast cancer, a noninvasive method for predictive prognosis and diagnosis was investigated using a 64Cu-labeled CD146-specific monoclonal antibody, YY146. CD146 expression was screened in human breast cancer cell lines using Western blotting. Binding ability was evaluated using flow cytometry and immunofluorescent staining. YY146 was conjugated with 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with 64Cu following standard procedures. Serial PET or PET/CT imaging was performed in orthotopic and metastatic breast cancer tumor models. Biodistribution was performed after the final time point of imaging. Finally, tissue immunofluorescent staining and hematoxylin and eosin (H&E) staining were performed on tumor tissues. The MDA-MB-435 cell line showed the highest CD146 expression level, whereas MCF-7 had the lowest level at the cellular level. ImmunoPET showed that MDA-MB-435 orthotopic tumors had high and clear radioactive accumulation after the administration of 64Cu-NOTA-YY146. The tumor uptake of 64Cu-NOTA-YY146 in MDA-MB-435 was significantly higher than that in MCF-7 and nonspecific IgG control groups (P < 0.01). Biodistribution verified the PET imaging results. For metastatic models, 64Cu-NOTA-YY146 allowed for the visualization of high radioactivity accumulation in metastatic MDA-MB-435 tumors, which was confirmed by ex vivo biodistribution of lung tissues. H&E staining proved the successful building of metastatic tumor models. Immunofluorescent staining verified the differential expression of CD146 in orthotopic tumors. Therefore, 64Cu-NOTA-YY146 could be used as an immunoPET probe to visualize CD146 in the breast cancer model and is potentially useful for cancer diagnosis, prognosis prediction, and monitoring therapeutic response.
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