Department of Neurology, CHU de Caen, Caen, France.
Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, 14000, Caen, France.
Eur J Nucl Med Mol Imaging. 2017 Aug;44(8):1383-1392. doi: 10.1007/s00259-017-3677-5. Epub 2017 Mar 18.
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-1α (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-1α), 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-1α, 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.
脑胶质瘤中的缺氧与肿瘤对放化疗的耐药性有关。然而，正电子发射断层扫描（PET）成像对缺氧的检测仍然具有挑战性，因此，生物标志物的验证非常重要。我们研究了 [18F]-FMISO 这种 PET 缺氧示踪剂摄取与其他缺氧和血管生成标志物之间的关系，并与患者的生存情况进行了关联。
在这项前瞻性单中心临床研究中，33 名脑胶质瘤患者（IV 级：n=24，III 级：n=3，II 级：n=6）在手术前进行了 [18F]-FMISO PET 和 MRI 检查，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，并根据是否摄取 [18F]-FMISO 将患者分为两组。手术后，对肿瘤标本进行 CAIX、VEGF、Ang2（实时定量 PCR）和 HIF-1α（免疫组化）的分子定量分析。
[18F]-FMISO PET 摄取与肿瘤分级密切相关，高级别胶质瘤（GB，IV 级）摄取较高。缺氧标志物（CAIX、HIF-1α）和血管生成标志物（VEGF、Ang2、rCBV）的表达在 [18F]-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-1α、CAIX、VEGF、Ang2 和 rCBV 的表达之间存在相关性（p<0.01）。无 [18F]-FMISO 摄取的患者的生存时间长于摄取阳性患者（对数秩检验，p<0.005）。
[18F]-FMISO PET 评估的肿瘤缺氧与分子水平上的缺氧标志物表达相关，并与血管生成有关。[18F]-FMISO 摄取是侵袭性肿瘤的标志，几乎总是高级别胶质瘤。我们的结果表明，[18F]-FMISO PET 可用于指导胶质瘤治疗，特别是放疗，因为缺氧是众所周知的耐药因素。
