Targeted imaging of tumor-associated M2 macrophages using a macromolecular contrast agent PG-Gd-NIR813.
Targeted imaging of tumor-associated M2 macrophages using a macromolecular contrast agent PG-Gd-NIR813.
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DOI：
10.1016/j.biomaterials.2010.05.001
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发表时间：
2010-09
期刊：
影响因子：
14
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Melancon MP;Lu W;Huang Q;Thapa P;Zhou D;Ng C;Li C
肿瘤相关巨噬细胞(TAMs)是包含多种亚型的多样性群体。M2巨噬细胞促进肿瘤生长和转移，部分是通过分泌广泛的促血管生成因子和生长因子。选择性去除M2巨噬细胞已被认为是一种新的抗癌治疗方法。在本研究中，我们合成了一种双磁光成像探针PG-Gd-NIR813，并将其应用于静脉注射后TAMS的无创检测。Pg-Gd-NIR813注射于荷C6肿瘤的裸鼠体内后，无论是在体内还是在体外，光学成像均显示肿瘤内聚合物造影剂的高摄取。T1加权磁共振成像结果显示PG-Gd-NIR813聚集到肿瘤坏死区，切除肿瘤的TUNEL染色证实了这一点。巨噬细胞清除剂处理后，肿瘤坏死区对PG-Gd-NIR813的摄取减少。免疫组织化学染色显示PG-Gd-NIR813与CD68(巨噬细胞标志物)和CD169(活化巨噬细胞标志物)共存，但不与CD163(居民性巨噬细胞)共存。结合近红外荧光成像和MRI，我们证实了Pg-Gd-NIR813在肿瘤中的蓄积是通过M2 TAMs介导的。因此，基于聚(L-谷氨酸)的试剂可能被用来成像针对M2 TAMs的抗肿瘤治疗的反应。此外，聚L-谷氨酸是一种很有前途的针对M2 TAMs的候选免疫治疗载体。
Tumor-associated macrophages (TAMs) are diverse population containing multiple subtypes. M2 macrophages promote tumor growth and metastasis, in part by secreting a wide range of proangiogenic factors and growth factors. Selective depletion of M2 macrophages has been evaluated as a novel approach to anti-cancer therapy. In this study, a dual magneto-optical imaging probe, PG-Gd-NIR813 was synthesized and evaluated for noninvasive assessment of TAMs after intravenous injection. PG-Gd-NIR813 injected in nude rats bearing C6 tumors showed high uptake of the polymeric contrast agent in the tumor at 1 and 48 h after injection both in vivo and ex vivo optical imaging. T1-weighted MR imaging results showed accumulation of PG-Gd-NIR813 into the tumor necrotic area, which was confirmed by TUNEL staining of resected tumors. The uptake of PG-Gd-NIR813 within tumor necrosis decreased after animals were treated by the macrophage depleting agent. Immunohistochemical staining demonstrated that PG-Gd-NIR813 colocalized with CD68 (marker for macrophages) and CD169 (marker for activated macrophages), but not with CD163 (residential macrophages). Using combined near-infrared fluorescence imaging and MRI, we demonstrated that the accumulation of PG-Gd-NIR813 in tumors was mediated through M2 TAMs. Therefore, poly(L-glutamic acid) based reagents could be potentially used to image response to antitumor therapies targeted at M2 TAMs. Furthermore, poly(L-glutamic acid) is a promising carrier for candidate immunotherapeutics targeting M2 TAMs.
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DOI：
10.1016/s0360-3016(00)00757-4
发表时间：
2000-11-01
影响因子：
7
作者：
Li, C;Ke, S;Wallace, S
通讯作者：
Wallace, S
影响因子：
82.9
作者：
Nagaraj, Srinivas;Gupta, Kapil;Gabrilovich, Dmitry I.
通讯作者：
Gabrilovich, Dmitry I.
影响因子：
4.8
作者：
Leimgruber, Antoine;Berger, Cedric;Pittet, Mikael J.
通讯作者：
Pittet, Mikael J.
影响因子：
11.5
作者：
Forssell, Johan;Oeberg, Ake;Palmqvist, Richard
通讯作者：
Palmqvist, Richard
DOI：
10.1093/jnci/90.21.1648
发表时间：
1998-11-04
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Joseph, IBJK;Isaacs, JT
通讯作者：
Isaacs, JT