Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models
Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models
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DOI：
10.1007/s00259-021-05544-4
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发表时间：
2021-09-01
影响因子：
9.1
通讯作者：
Kuge，Yuji
中科院分区：
文献类型：
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作者：
Bo，Tomoki;Yasui，Hironobu;Kuge，Yuji
目的艾日布林是一种微管动力学抑制剂，通过其对肿瘤血管的重塑作用而发挥抗肿瘤作用。然而，艾日布林改善肿瘤缺氧的程度影响放射敏感性仍不清楚。我们利用1-（2，2-dihydroxymethyl-3-18F-fluoropropyl）-2-nitroimidazole（18F-DiFA），一种新的缺氧PET探针，研究艾日布林对肿瘤缺氧的影响，并评估艾日布林治疗过程中的放射敏感性。给药后分别注射18F-DiFA和哌莫硝唑，分析肿瘤缺氧区域。对于接受放射联合治疗的组，在局部X射线照射肿瘤之前进行18F-DiFA PET/CT成像。照射后每隔一天测量一次肿瘤大小。ResultsEribulin显着降低18F-DiFA积累水平的剂量依赖性方式。此外，艾日布林对18F-DiFA蓄积水平的降低在给药后7天最为显著。这些结果也支持减少pimonidazole阳性缺氧区。与对照组、单纯放疗组和单纯药物组相比，联合治疗组肿瘤生长明显延缓。重要的是，照射后的肿瘤生长呈负相关与18F-DiFA accumulation.ConclusionThese结果表明，18F-DiFA PET/CT清楚地检测到艾日布林诱导的肿瘤氧合和艾日布林有效地提高了抗肿瘤活性的辐射，通过改善肿瘤氧合。
PurposeEribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-18F-fluoropropyl)-2-nitroimidazole (18F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment.MethodsMice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with18F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation,18F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation.ResultsEribulin significantly reduced18F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in18F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with18F-DiFA accumulation.ConclusionThese results demonstrated that18F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.