Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
AJNR Am J Neuroradiol. 2013 Jan;34(1):92-9. doi: 10.3174/ajnr.A3159. Epub 2012 Jun 14.
Hypoxic tissue evaluation in glioma is important for predicting treatment response and establishing antihypoxia therapy. In this preliminary study, (62)Cu-ATSM PET was used to determine its validity as a biomarker for distinguishing tumor grade and tissue hypoxia.
(62)Cu-ATSM PET was performed in 22 patients with glioma, and the (62)Cu-ATSM SUV(max) and T/B ratio were semiquantitatively evaluated. (62)Cu-ATSM uptake distribution was qualitatively evaluated and compared with MR imaging findings. HIF-1α expression, a hypoxia marker, was compared with (62)Cu-ATSM uptake values.
The (62)Cu-ATSM SUV(max) and T/B ratio were significantly higher in grade IV than in grade III gliomas (P = .014 and .018, respectively), whereas no significant differences were found between grade III and grade II gliomas. At a T/B ratio cutoff threshold of 1.8, (62)Cu-ATSM uptake was predictive of HIF-1α expression, with 92.3% sensitivity and 88.9% specificity. The mean T/B ratio was also significantly higher in HIF-1α-positive glioma tissue than in HIF-1α-negative tissue (P = .001). Using this optimal threshold of T/B ratio, (62)Cu-ATSM PET showed regional uptake in 61.9% (13/21) of tumors within the contrast-enhanced region on MR imaging, which was significantly correlated with presence of a necrotic component (P = .002).
Our results demonstrated that (62)Cu-ATSM uptake is relatively high in grade IV gliomas and correlates with the MR imaging findings of necrosis. Moreover, the (62)Cu-ATSM T/B ratio showed significant correlation with HIF-1α expression. Thus, (62)Cu-ATSM appears to be a suitable biomarker for predicting highly malignant grades and tissue hypoxia in patients with glioma.
评估脑胶质瘤的缺氧组织对于预测治疗反应和建立抗缺氧治疗非常重要。在这项初步研究中，我们使用 62Cu-ATSM PET 来确定其作为区分肿瘤分级和组织缺氧的生物标志物的有效性。
对 22 例脑胶质瘤患者进行 62Cu-ATSM PET 检查，对 62Cu-ATSM SUV(max)和 T/B 比值进行半定量评估。对 62Cu-ATSM 摄取分布进行定性评估，并与磁共振成像结果进行比较。比较缺氧标志物 HIF-1α表达与 62Cu-ATSM 摄取值。
4 级胶质瘤的 62Cu-ATSM SUV(max)和 T/B 比值明显高于 3 级胶质瘤（P =.014 和.018），而 3 级和 2 级胶质瘤之间无显著差异。当 T/B 比值截断值为 1.8 时，62Cu-ATSM 摄取可预测 HIF-1α表达，具有 92.3%的敏感性和 88.9%的特异性。HIF-1α 阳性胶质瘤组织的平均 T/B 比值也明显高于 HIF-1α 阴性组织（P =.001）。使用此最佳 T/B 比值阈值，62Cu-ATSM PET 在磁共振成像增强区域内的 61.9%（13/21）肿瘤中显示出区域性摄取，与坏死成分的存在显著相关（P =.002）。
我们的结果表明，4 级脑胶质瘤中 62Cu-ATSM 摄取相对较高，与坏死的磁共振成像表现相关。此外，62Cu-ATSM 的 T/B 比值与 HIF-1α 表达有显著相关性。因此，62Cu-ATSM 似乎是预测脑胶质瘤患者高度恶性分级和组织缺氧的合适生物标志物。
