Theranostics 2017; 7(17):4276-4288. doi:10.7150/thno.20999

Research Paper

Noninvasive Imaging of CD206-Positive M2 Macrophages as an Early Biomarker for Post-Chemotherapy Tumor Relapse and Lymph Node Metastasis

Chenran Zhang1, Xinhe Yu1, Liquan Gao1, Yang Zhao1, Jianhao Lai1, Dehua Lu1, Rui Bao1, Bing Jia1, 2, Lijun Zhong2, Fan Wang1, 3, Zhaofei Liu1✉

1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
2. Medical and Healthy Analytical Center, Peking University, Beijing 100191, China;
3. Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

Tumor relapse after initial regression post-chemotherapy is a major challenge in cancer treatment, as it usually leads to local-regional recurrence or inoperable distant metastasis. M2 macrophages diminish the tumor-inhibitory effect of chemotherapy and correlate with distant metastasis and poor prognosis. In this study, we investigated whether molecular imaging of M2 macrophages could serve as an early biomarker for tumor relapse after chemotherapy and tumor lymph node metastasis in preclinical mouse models. Methods: We developed M2 macrophage-targeted probes for near-infrared fluorescence (NIRF) imaging and single-photon emission computed tomography (SPECT) using an anti-CD206 monoclonal antibody. The specific targeting capacity and potential applications of the NIRF and SPECT probes were investigated in subcutaneous tumor and lymph node metastasis models of 4T1 murine breast cancer. Results: M2 macrophage infiltration was significantly increased in the 4T1 tumors that later underwent relapse but not in non-relapsing 4T1 tumors after cyclophosphamide treatment. Through NIRF imaging and SPECT using our synthesized probes, the infiltration of M2 macrophages in relapsing tumors and tumor lymph node metastasis could be sensitively detected. Importantly, early prediction of tumor relapse by molecular imaging of M2 macrophages resulted in an effective eradication of tumors upon combination with additional radiotherapy. Conclusion: Our findings demonstrate that M2 macrophage-targeted imaging allows for noninvasively predicting post-chemotherapy tumor relapse and sensitively detecting the metastatic lymph nodes in vivo. This imaging strategy could provide a better understanding of cancer progression, enable early prediction of tumor resistance, and have implications on the rational design of cancer therapeutics.

Keywords: M2 macrophage, CD206, Molecular imaging, SPECT, Tumor resistance.

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How to cite this article:
Zhang C, Yu X, Gao L, Zhao Y, Lai J, Lu D, Bao R, Jia B, Zhong L, Wang F, Liu Z. Noninvasive Imaging of CD206-Positive M2 Macrophages as an Early Biomarker for Post-Chemotherapy Tumor Relapse and Lymph Node Metastasis. Theranostics 2017; 7(17):4276-4288. doi:10.7150/thno.20999. Available from http://www.thno.org/v07p4276.htm