Spence Alexander M, Muzi Mark, Swanson Kristin R, O'Sullivan Finbarr, Rockhill Jason K, Rajendran Joseph G, Adamsen Tom C H, Link Jeanne M, Swanson Paul E, Yagle Kevin J, Rostomily Robert C, Silbergeld Daniel L, Krohn Kenneth A
Department of Neurology, University of Washington, Seattle, Washington 98195, USA.
Clin Cancer Res. 2008 May 1;14(9):2623-30. doi: 10.1158/1078-0432.CCR-07-4995.
Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [(18)F]fluoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival.
Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [(18)F]fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum T/B values (T/B(max)) were determined from the pixel with the highest uptake.
Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/B(max) ratios greater than the median (P < or = 0.001). In univariate analyses, greater HV or tumor T/B(max) were associated with shorter TTP or survival (P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/B(max)), magnetic resonance imaging (MRI) T1Gd volume, age, and Karnovsky performance score reached significance only for HV (or T/B(max); P < 0.03).
The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.
缺氧与放疗和化疗耐药相关，并激活支持细胞存活和迁移的转录因子。我们用[（18）F]氟米索硝唑正电子发射断层扫描测量多形性胶质母细胞瘤放疗前缺氧肿瘤的体积和最大缺氧水平，以评估它们对疾病进展时间（TTP）或生存期的影响。
对22例患者在活检前或切除与开始放疗之间进行研究。每例患者在静脉注射7mCi[（18）F]氟米索硝唑后2小时进行20分钟的发射扫描。成像期间采集的静脉血样本用于计算组织与血液浓度（T/B）比值。T/B值高于1.2的肿瘤体积定义为缺氧体积（HV）。从摄取最高的像素确定最大T/B值（T/B（max））。
Kaplan-Meier曲线显示，肿瘤含有HV或肿瘤T/B（max）比值大于中位数的患者，其TTP和生存期较短（P≤0.001）。在单因素分析中，更大的HV或肿瘤T/B（max）与更短的TTP或生存期相关（P<0.002）。针对协变量HV（或T/B（max））、磁共振成像（MRI）T1Gd体积、年龄和卡诺夫斯基表现评分进行的生存和TTP多因素分析仅对HV（或T/B（max））有显著意义（P<0.03）。
多形性胶质母细胞瘤放疗前缺氧的体积和强度与较差的TTP和生存期密切相关。这种成像类型可纳入新的治疗策略，以更积极地针对多形性胶质母细胞瘤中的缺氧情况，并且可用于评估治疗结果。
