[18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis
[18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis
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DOI：
10.1007/s00259-017-3677-5
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发表时间：
2017-08-01
影响因子：
9.1
通讯作者：
Guillamo, Jean-Sebastien
中科院分区：
文献类型：
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作者：
Bekaert, Lien;Valable, Samuel;Guillamo, Jean-Sebastien
脑胶质瘤中的缺氧与肿瘤对放疗和化疗的抵抗有关。然而，缺氧的正电子发射断层扫描（PET）成像仍然具有挑战性，因此，生物标志物的验证非常重要。我们研究了PET缺氧示踪剂[18 F]-FMISO和其他缺氧和血管生成标记物的摄取与患者存活率之间的关系。在这项前瞻性单中心临床研究中，33例胶质瘤患者（IV级：n = 24，III级：n = 3，II级：n = 6）在手术前接受了[18 F]-FMISO PET和MRI，包括相对脑血容量（rCBV）图。计算最大标准化摄取值（SUVmax）和缺氧体积，根据[18 F]-FMISO摄取的存在或不存在定义两组患者。手术后，对肿瘤标本进行CAIX、VEGF、Ang 2（rt-qPCR）和HIF-1 α（免疫组织化学）的分子定量。[18 F]-FMISO PET摄取与肿瘤分级密切相关，胶质母细胞瘤中的摄取较高（GB，IV级）。缺氧生物标志物（CAIX，HIF-1 α）和血管生成标志物（VEGF，Ang 2，rCBV）的表达在[18 F]-FMISO摄取组中显著更高。我们发现缺氧程度（缺氧体积和SUVmax）与HIF-1 α、CAIX、VEGF、Ang 2和rCBV的表达之间存在相关性（p < 0.01）。未摄取[18 F]-FMISO的患者比摄取阳性的患者具有更长的存活时间（对数秩，p < 0.005）。通过[18 F]-FMISO PET评估的肿瘤缺氧在分子水平上与缺氧标志物的表达相关，并且与血管生成相关。[18F]-FMISO摄取是侵袭性肿瘤的标志，几乎总是胶质母细胞瘤。我们的研究结果强调，[18 F]-FMISO PET可能有助于指导胶质瘤治疗，特别是放射治疗，因为缺氧是一个众所周知的耐药因素。
Hypoxia in gliomas is associated with tumor resistance to radio- and chemotherapy. However, positron emission tomography (PET) imaging of hypoxia remains challenging, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival.In this prospective single center clinical study, 33 glioma patients (grade IV: n = 24, III: n = 3, and II: n = 6) underwent [18F]-FMISO PET and MRI including relative cerebral blood volume (rCBV) maps before surgery. Maximum standardized uptake values (SUVmax) and hypoxic volume were calculated, defining two groups of patients based on the presence or absence of [18F]-FMISO uptake. After surgery, molecular quantification of CAIX, VEGF, Ang2 (rt-qPCR), and HIF-1 alpha (immunohistochemistry) were performed on tumor specimens.[18F]-FMISO PET uptake was closely linked to tumor grade, with high uptake in glioblastomas (GB, grade IV). Expression of biomarkers of hypoxia (CAIX, HIF-1 alpha), and angiogenesis markers (VEGF, Ang2, rCBV) were significantly higher in the [18F]-FMISO uptake group. We found correlations between the degree of hypoxia (hypoxic volume and SUVmax) and expression of HIF-1 alpha, CAIX, VEGF, Ang2, and rCBV (p < 0.01). Patients without [18F]-FMISO uptake had a longer survival time than uptake positive patients (log-rank, p < 0.005).Tumor hypoxia as evaluated by [18F]-FMISO PET is associated with the expression of hypoxia markers on a molecular level and is related to angiogenesis. [18F]-FMISO uptake is a mark of an aggressive tumor, almost always a glioblastoma. Our results underline that [18F]-FMISO PET could be useful to guide glioma treatment, and in particular radiotherapy, since hypoxia is a well-known factor of resistance.