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Spatial and quantitative mapping of glycolysis and hypoxia in glioblastoma as a predictor of radiotherapy response and sites of relapse.
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : 2020-02-05 , DOI: 10.1007/s00259-020-04706-0
Antoine Leimgruber 1, 2 , Kevin Hickson 1, 3 , Sze Ting Lee 1, 4, 5 , Hui K Gan 2, 5 , Lawrence M Cher 6 , John I Sachinidis 1 , Graeme J O'Keefe 1 , Andrew M Scott 1, 4, 5, 6
Affiliation  

INTRODUCTION Tumor hypoxia is a centerpiece of disease progression mechanisms such as neoangiogenesis or aggressive hypoxia-resistant malignant cells selection that impacts on radiotherapy strategies. Early identification of regions at risk for recurrence and prognostic-based classification of patients is a necessity to devise tailored therapeutic strategies. We developed an image-based algorithm to spatially map areas of aerobic and anaerobic glycolysis (Glyoxia). METHODS 18F-FDG and 18F-FMISO PET studies were used in the algorithm to produce DICOM-co-registered representations and maximum intensity projections combined with quantitative analysis of hypoxic volume (HV), hypoxic glycolytic volume (HGV), and anaerobic glycolytic volume (AGV) with CT/MRI co-registration. This was applied to a prospective clinical trial of 10 glioblastoma patients with post-operative, pre-radiotherapy, and early post-radiotherapy 18F-FDG and 18F-FMISO PET and MRI studies. RESULTS In the 10 glioblastoma patients (5M:5F; age range 51-69 years), 14/18 18F-FMISO PET studies showed detectable hypoxia. Seven patients survived to complete post-radiotherapy studies. The patient with the longest overall survival showed non-detectable hypoxia in both pre-radiotherapy and post-radiotherapy 18F-FMISO PET. The three patients with increased HV, HGV, and AGV volumes after radiotherapy showed 2.8 months mean progression-free interval vs. 5.9 months for the other 4 patients. These parameters correlated at that time point with progression-free interval. Parameters combining hypoxia and glycolytic information (i.e., HGV and AGV) showed more prominent variation than hypoxia-based information alone (HV). Glyoxia-generated images were consistent with disease relapse topology; in particular, one patient had distant relapse anticipated by HV, HGV, and AGV maps. CONCLUSION Spatial mapping of aerobic and anaerobic glycolysis allows unique information on tumor metabolism and hypoxia to be evaluated with PET, providing a greater understanding of tumor biology and potential response to therapy.

中文翻译:

胶质母细胞瘤中糖酵解和缺氧的空间和定量映射作为放射治疗反应和复发部位的预测因子。

引言 肿瘤缺氧是疾病进展机制的核心,例如影响放射治疗策略的新血管生成或侵袭性抗缺氧恶性细胞选择。早期识别有复发风险的区域和基于预后的患者分类是制定量身定制的治疗策略的必要条件。我们开发了一种基于图像的算法来空间映射有氧和无氧糖酵解 (Glyoxia) 的区域。方法 在算法中使用 18F-FDG 和 18F-FMISO PET 研究,结合缺氧体积 (HV)、低氧糖酵解体积 (HGV) 和无氧糖酵解体积的定量分析,产生 DICOM 共同注册的表示和最大强度预测。 AGV) 与 CT/MRI 联合配准。这被应用于 10 名胶质母细胞瘤患者的前瞻性临床试验,包括术后、放疗前和放疗后早期 18F-FDG 和 18F-FMISO PET 和 MRI 研究。结果 在 10 名胶质母细胞瘤患者(5M:5F;年龄范围 51-69 岁)中,14/18 18F-FMISO PET 研究显示可检测到缺氧。七名患者存活到完成放射治疗后的研究。总生存期最长的患者在放疗前和放疗后的 18F-FMISO PET 中均显示出不可检测的缺氧。放疗后 HV、HGV 和 AGV 体积增加的三名患者显示平均无进展间隔为 2.8 个月,而其他 4 名患者为 5.9 个月。这些参数在那个时间点与无进展间隔相关。结合缺氧和糖酵解信息的参数(即,HGV 和 AGV) 比仅基于缺氧的信息 (HV) 表现出更显着的变化。Glyoxia 生成的图像与疾病复发拓扑一致;特别是,一名患者的 HV、HGV 和 AGV 图预计会出现远处复发。结论 有氧和无氧糖酵解的空间映射允许使用 PET 评估有关肿瘤代谢和缺氧的独特信息,从而更好地了解肿瘤生物学和对治疗的潜在反应。
更新日期:2020-02-06
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