Molecular imaging of tumor-infiltrating macrophages in a preclinical mouse model of breast cancer.
Molecular imaging of tumor-infiltrating macrophages in a preclinical mouse model of breast cancer.
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乳腺癌临床前小鼠模型中肿瘤浸润巨噬细胞的分子成像
作者：
Sun X;Gao D;Gao L;Zhang C;Yu X;Jia B;Wang F;Liu Z
大量证据表明，肿瘤相关巨噬细胞（TAMs）在多种人类肿瘤的增殖、侵袭、血管生成和转移中起关键作用。在这项研究中，我们研究了是否近红外荧光（NIRF）成像使用巨噬细胞甘露糖受体（MMR; CD 206）靶向剂可用于非侵入性可视化和量化的变化在体内的TAM。制备了CD 206靶向NIRF试剂Dye-anti-CD 206，并在体外和体内进行了表征。通过使用NIRF成像，我们能够对4 T1小鼠乳腺癌模型中的肿瘤浸润性巨噬细胞进行非侵入性成像。重要的是，纵向NIRF成像显示了巨噬细胞对唑来膦酸（ZA）治疗的反应。然而，单独的ZA不导致4 T1肿瘤生长的抑制。因此，我们在小鼠模型中将抗巨噬细胞ZA疗法和肿瘤细胞毒性多西他赛（DTX）疗法组合。结果表明，该组合策略可以显著抑制肿瘤生长以及肿瘤向肺的转移。基于这些发现，我们得出结论，CD 206靶向分子成像可以灵敏地检测肿瘤浸润巨噬细胞的动态变化，巨噬细胞清除和细胞毒治疗的组合是一个有前途的策略，有效地治疗实体瘤。
Significant evidence has indicated that tumor-associated macrophages (TAMs) play a critical role in the proliferation, invasion, angiogenesis, and metastasis of a variety of human carcinomas. In this study, we investigated whether near-infrared fluorescence (NIRF) imaging using a macrophage mannose receptor (MMR; CD206)-targeting agent could be used to noninvasively visualize and quantify changes in TAMs in vivo. The CD206-targeting NIRF agent, Dye-anti-CD206, was prepared and characterized in vitro and in vivo. By using NIRF imaging, we were able to noninvasively image tumor-infiltrating macrophages in the 4T1 mouse breast cancer model. Importantly, longitudinal NIRF imaging revealed the depletion of macrophages in response to zoledronic acid (ZA) treatment. However, ZA alone did not lead to the inhibition of 4T1 tumor growth. We therefore combined anti-macrophage ZA therapy and tumor cytotoxic docetaxel (DTX) therapy in the mouse model. The results demonstrated that this combination strategy could significantly inhibit tumor growth as well as tumor metastasis to the lungs. Based on these findings, we concluded that CD206-targeted molecular imaging can sensitively detect the dynamic changes in tumor-infiltrating macrophages, and that the combination of macrophage depletion and cytotoxic therapy is a promising strategy for the effective treatment of solid tumors.
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