Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models
Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models
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DOI：
10.1186/s13550-019-0521-x
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发表时间：
2019-06-03
期刊：
影响因子：
3.2
通讯作者：
Kuge, Yuji
中科院分区：
文献类型：
--
作者：
Zhao, Songji;Yu, Wenwen;Kuge, Yuji
研究背景艾日布林是一种微管动力学抑制剂，通过其抗血管活性和重塑肿瘤血管而显示出对多种实体瘤的抗肿瘤作用。F-18-氟咪唑（F-18-FMISO）是用于肿瘤缺氧成像的最广泛使用的PET探针。在这项研究中，我们利用F-18-FMISO澄清艾日布林对肿瘤缺氧条件的影响，比较组织学findings.Material和methodsMice荷人癌细胞异种移植物腹腔内给予单剂量的艾日布林（0.3或1.0mg/kg）或生理盐水。治疗后三天，给小鼠注射F-18-FMISO和哌莫硝唑（免疫组织化学的缺氧标志物），并测定肿瘤间F-18-FMISO积累水平和组织学特征。在艾日布林（0.3mg/kg，i. p.）治疗前后进行PET/CT。结果艾日布林治疗组F-18-FMISO蓄积水平和pimonidazole阳性缺氧面积百分比显著降低，而微血管数量增加。PET/CT证实，F-18-FMISO在肿瘤中的分布减少后eribulin treatment.ConclusionsUsing F-18-FMISO，我们证明了消除肿瘤缺氧条件eribulin治疗，伴随着微血管密度的增加。这些发现表明，使用F-18-FMISO的PET成像可能为检测接受艾日布林治疗的临床患者的早期治疗反应提供可能性。
BackgroundEribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. F-18-Fluoromisonidazole (F-18-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized F-18-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings.Material and methodsMice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0mg/kg) or saline. Three days after the treatment, mice were injected with F-18-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral F-18-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3mg/kg, i.p.).ResultsThe F-18-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that F-18-FMISO distribution in the tumor was decreased after the eribulin treatment.ConclusionsUsing F-18-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using F-18-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.