Noninvasive Imaging of CD206-Positive M2 Macrophages as an Early Biomarker for Post-Chemotherapy Tumor Relapse and Lymph Node Metastasis.
Noninvasive Imaging of CD206-Positive M2 Macrophages as an Early Biomarker for Post-Chemotherapy Tumor Relapse and Lymph Node Metastasis.
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作者：
Zhang C;Yu X;Gao L;Zhao Y;Lai J;Lu D;Bao R;Jia B;Zhong L;Wang F;Liu Z
化疗后初始消退后的肿瘤复发是癌症治疗中的主要挑战，因为它通常导致局部区域复发或不可手术的远处转移。M2巨噬细胞减弱化疗的肿瘤抑制作用，并与远处转移和预后不良相关。在这项研究中，我们研究了M2巨噬细胞的分子成像是否可以作为临床前小鼠模型化疗后肿瘤复发和肿瘤淋巴结转移的早期生物标志物。研究方法：我们使用抗CD206单克隆抗体开发了M2巨噬细胞靶向探针，用于近红外荧光（NIRF）成像和单光子发射计算机断层扫描（SPECT）。在4T1小鼠乳腺癌皮下肿瘤和淋巴结转移模型中研究了NIRF和SPECT探针的特异性靶向能力和潜在应用。结果如下：M2巨噬细胞浸润显着增加，在4T1肿瘤，后来经历复发，但没有在非复发4T1肿瘤环磷酰胺治疗后。用我们合成的探针进行NIRF显像和SPECT显像，可以灵敏地检测M2巨噬细胞在复发肿瘤中的浸润和肿瘤淋巴结转移。重要的是，通过M2巨噬细胞的分子成像对肿瘤复发的早期预测在与额外的放射治疗组合后导致肿瘤的有效根除。结论：我们的研究结果表明，M2巨噬细胞靶向成像允许非侵入性地预测化疗后肿瘤复发和灵敏地检测体内转移淋巴结。这种成像策略可以更好地了解癌症进展，能够早期预测肿瘤耐药性，并对癌症治疗的合理设计产生影响。
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.
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影响因子：
--
作者：
Blanchard, DK;Donohue, JH;Grant, CS
通讯作者：
Grant, CS
影响因子：
12.4
作者：
Devey, Luke;Ferenbach, David;Wigmore, Stephen J.
通讯作者：
Wigmore, Stephen J.
影响因子：
6.2
作者：
Green, JR
通讯作者：
Green, JR
影响因子：
11.2
作者：
Hughes R;Qian BZ;Rowan C;Muthana M;Keklikoglou I;Olson OC;Tazzyman S;Danson S;Addison C;Clemons M;Gonzalez-Angulo AM;Joyce JA;De Palma M;Pollard JW;Lewis CE
通讯作者：
Lewis CE
影响因子：
12.4
作者：
Gao L;Zhang C;Gao D;Liu H;Yu X;Lai J;Wang F;Lin J;Liu Z
通讯作者：
Liu Z