Jiang Chong, Cai Huawei, Peng Xiaodong, Zhang Ping, Wu Xiaoai, Tian Rong
1 Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.
2 Department of Clinical Immunology, West China Hospital, Sichuan University, Chengdu, China.
Mol Imaging. 2017 Jan 1;16:1536012116689499. doi: 10.1177/1536012116689499.
Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs), but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM), a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7), and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.
甘露糖受体被认为是M2型肿瘤相关巨噬细胞（TAM）的一个标志，但它在TAM中的应用鲜有报道。因此，将甘露糖受体的高亲和力配体脱氧甘露糖（DM）用近红外染料花菁7（Cy7）进行标记，并在体外和体内评估其对TAM进行靶向成像的可行性。合成了Cy7-DM，并评估了其与体外诱导的TAM的结合亲和力、体内异种移植瘤小鼠模型中的全身成像以及解剖组织中的细胞定位。我们证明了Cy7-DM在肿瘤组织中被诱导的M2巨噬细胞和TAM大量摄取。体内近红外实时成像通过Cy7-DM成像在肿瘤病灶而非炎症部位可视化了大量TAM，并且在成像的1至8小时内，肿瘤中Cy7-DM信号的数量显著高于炎症部位。我们的结果表明，甘露糖可以快速且特异性地靶向TAM，是富含TAM肿瘤靶向诊断的一个有前景的候选物。
