TY - JOUR
T1 - Targeted imaging of tumor-associated M2 macrophages using a macromolecular contrast agent PG-Gd-NIR813
AU - Melancon, Marites P.
AU - Lu, Wei
AU - Huang, Qian
AU - Thapa, Prakash
AU - Zhou, Dapeng
AU - Ng, Chaan
AU - Li Chun, C.
N1 - Funding Information:
We thank Dawn Chalaire for editing the manuscript. This work was supported in part by a grant from the National Institutes of Health ( R01 CA119387 ), a Seed Grant through the Alliance for NanoHealth by the Department of Army Telemedicine and Advanced Technology Research Center ( W81XWH-07-2-0101 ), a grant from John S. Dunn, Sr. Distinguished Chair in Diagnostic Imaging (to Dr. Murphy) by the John S. Dunn Foundation, a start-up fund by M.D. Anderson Cancer Center to DZ, and an Odyssey Fellowship (to MPM). The Odyssey Fellowship is supported by the Odyssey Program and the Cockrell Foundation for Scientific Achievement at The University of Texas M. D. Anderson Cancer Center. We also acknowledge the NCI Cancer Center Support Grant CA016672 for the support of our small animal facility and small animal imaging facility.
PY - 2010/9
Y1 - 2010/9
N2 - 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 non-invasive 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 magnetic resonance imaging (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.
AB - 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 non-invasive 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 magnetic resonance imaging (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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U2 - 10.1016/j.biomaterials.2010.05.001
DO - 10.1016/j.biomaterials.2010.05.001
M3 - Article
C2 - 20537382
AN - SCOPUS:77953959072
SN - 0142-9612
VL - 31
SP - 6567
EP - 6573
JO - Biomaterials
JF - Biomaterials
IS - 25
ER -