Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy
Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy
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Src 抑制后肿瘤特征的分子成像用于指导达沙替尼联合治疗
DOI：
10.2967/jnumed.115.158881
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发表时间：
2016-02-01
影响因子：
9.3
通讯作者：
Liu, Zhaofei
中科院分区：
文献类型：
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作者：
Gao, Liquan;Liu, Hao;Liu, Zhaofei
与癌症治疗干预相关的关键生物标志物的无创、实时、定量测量可以更好地了解癌症生物学。在这项研究中，我们探讨了结合多种分子成像方法是否可以用于指导达沙替尼抗src治疗，并有助于合理设计联合治疗方案。方法：对肿瘤小鼠模型进行达沙替尼治疗前后的生物发光成像、18F-FDG PET、整合素αvβ3靶向SPECT/CT、血管内皮生长因子靶向近红外荧光成像。结果：达沙替尼治疗肿瘤与对照组相比，生物发光成像信号和18F-FDG肿瘤摄取无显著差异。然而，在达沙替尼治疗的肿瘤中，99mT-3PRGD2（整合素αvβ3特异性）和dylight755 -雷尼单抗（血管内皮生长因子特异性）的摄取明显低于对照肿瘤。体外研究证实了达沙替尼的抗血管生成作用，但表明缺乏细胞毒性。达沙替尼加细胞毒性多西他赛在体内引起了显著的协同肿瘤生长抑制。结论：通过多种成像方法可视化src抑制后肿瘤特征有助于体内肿瘤生物标志物的敏感和定量测量，从而有助于达沙替尼联合治疗的合理设计。
Noninvasive, real-time, quantitative measurement of key biomarkers associated with cancer therapeutic interventions could provide a better understanding of cancer biology. We investigated in this study whether incorporating multiple molecular imaging approaches could be used to guide dasatinib anti-Src therapy and aid in the rational design of a combination therapy regimen. Methods: Bioluminescence imaging, 18F-FDG PET, integrin αvβ3–targeted SPECT/CT, and vascular endothelial growth factor–targeted near-infrared fluorescence imaging were performed before and after dasatinib treatment in a tumor mouse model. Results: There was no significant difference in the bioluminescence imaging signal or 18F-FDG tumor uptake in dasatinib-treated tumors compared with the control tumors. However, the uptake of 99mT-3PRGD2 (integrin αvβ3–specific) and DyLight755-ranibizumab (vascular endothelial growth factor–specific) in the dasatinib-treated tumors was significantly lower than that in the control tumors. In vitro studies confirmed the antiangiogenic effects of dasatinib but indicated a lack of cytotoxicity. Dasatinib plus cytotoxic docetaxel elicited marked synergistic tumor growth inhibition in vivo. Conclusion: Visualization of post-Src inhibition tumor signatures through multiple imaging approaches facilitates sensitive and quantitative measurement of cancer biomarkers in vivo, thus aiding in the rational design of dasatinib combination therapy.