The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy.
The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy.
复制标题
通过FDG PET/CT评估的肾细胞癌中葡萄糖积累的加速表明，抗酪氨酸激酶抑制剂治疗的耐药性。
DOI：
10.1186/s12885-016-3044-0
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发表时间：
2017-01-09
期刊：
影响因子：
3.8
通讯作者：
Yao M
中科院分区：
文献类型：
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作者：
Nakaigawa N;Kondo K;Ueno D;Namura K;Makiyama K;Kobayashi K;Shioi K;Ikeda I;Kishida T;Kaneta T;Minamimoto R;Tateishi U;Inoue T;Yao M
靶向血管生成的酪氨酸激酶抑制剂（TKI）可改善转移性肾细胞癌（RCC）患者的预后，但其效果是暂时的。为了了解RCC获得对TKI耐药的机制，我们通过FDG PET/CT研究了RCC中葡萄糖蓄积的变化，当他们对TKI表现出疾病进展（PD）时。我们通过162 PET/CT连续监测了38例接受TKI治疗的RCC患者的FDG蓄积，直到他们被判定为PD。测量组织FDG蓄积率的简化指标标准化摄取值（SUV），并分析最大SUV最大值（个体患者最高SUV）的序列变化。此外，分析了葡萄糖转运蛋白1（GLUT-1）及其相关蛋白在低氧培养的786-O细胞中的表达。10例肾细胞癌患者在TKI治疗后FDG蓄积加速，很快就出现PD。TKI抑制FDG蓄积的28例RCC患者无进展生存期较长（3.6个月vs 6.5个月，P = 0.0026），但大多数病例（96%）的抑制是暂时的，当肿瘤表现为PD时，FDG蓄积加速。有趣的是，在一半的病例中，PD时的FDG蓄积高于TKI治疗前。FDG积累的加速受到抑制，以下处理的哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂。体外实验表明，在低氧条件下存活的RCC细胞中，GLUT-1的表达通过mTOR途径增加。通过FDG PET/CT评估的RCC中依赖于mTOR的葡萄糖蓄积加速表明获得了对TKI的耐药性。FDG PET/CT有可能作为一种评估方法，不仅监测TKI治疗期间RCC的初始缓解，还监测其后续状态。 UMIN 0000008141，2012年6月11日。本试验进行了回顾性登记。
Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed. The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway. The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment. UMIN0000008141, 11 Jun 2012. This trial was retrospectively registered.