Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy.
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy.
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DOI：
10.1038/s41598-021-90662-0
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发表时间：
2021-05-27
影响因子：
4.6
通讯作者：
Bernaudin M
中科院分区：
文献类型：
--
作者：
Corroyer-Dulmont A;Valable S;Fantin J;Chatre L;Toutain J;Teulier S;Bazille C;Letissier E;Levallet J;Divoux D;Ibazizène M;Guillouet S;Perrio C;Barré L;Serres S;Sibson NR;Chapon F;Levallet G;Bernaudin M
肺癌患者经常发生脑转移（BM）。尽管积极的治疗包括神经外科手术和外部放疗，总体生存率仍然很低。目前迫切需要进一步确定脑脊髓瘤微环境中可能导致放疗抵抗（RT）的因素，如缺氧。在这里，缺氧首先在28例非小细胞肺癌（NSCLC） BM患者的活检中进行评估，使用CA-IX免疫染色。通过脑内注射肿瘤细胞（H2030-Br3M, H1915）到皮质和纹状体，或心内注射肿瘤细胞（H2030-Br3M）诱导的不同临床前NSCLC BM模型，也进行了缺氧表征（吡莫硝唑，CA-IX和HIF-1α）。此外，[18F]-FMISO-PET和氧饱和度定位- mri （SatO2-MRI）在脑内BM模型中进一步表征肿瘤缺氧，并评估缺氧图像引导rt （HIGRT）的潜力。观察RT对BM （[18F]-FLT-PET）增殖、肿瘤体积及总生存期的影响。我们发现，无论是临床前还是临床，缺氧都是肺癌脑转移的一个主要但异质性的特征。基于在脑内诱导模型中观察到的皮质和纹状体转移之间的缺氧异质性，HIGRT在肿瘤控制和动物存活方面显示出显著的潜力。这些结果共同强调了缺氧是肺癌脑转移的标志，以及HIGRT在更好地控制肿瘤生长方面的价值。
Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth.
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DOI：
10.1007/s00259-015-3225-0
发表时间：
2016-04-01
影响因子：
9.1
作者：
Corroyer-Dulmont, Aurelien;Peres, Elodie A.;Valable, Samuel
通讯作者：
Valable, Samuel
影响因子：
2.6
作者：
Ambrosio MR;Di Serio C;Danza G;Rocca BJ;Ginori A;Prudovsky I;Marchionni N;Del Vecchio MT;Tarantini F
通讯作者：
Tarantini F
影响因子：
6.3
作者：
Chakhoyan, Ararat;Corroyer-Dulmont, Aurelien;Valable, Samuel
通讯作者：
Valable, Samuel
DOI：
10.1007/s00259-017-3677-5
发表时间：
2017-08-01
影响因子：
9.1
作者：
Bekaert, Lien;Valable, Samuel;Guillamo, Jean-Sebastien
通讯作者：
Guillamo, Jean-Sebastien
影响因子：
5
作者：
Berghoff, A. S.;Ilhan-Mutlu, A.;Preusser, M.
通讯作者：
Preusser, M.