Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma
Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma
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DOI：
10.1007/s00259-010-1645-4
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发表时间：
2011-03-01
影响因子：
9.1
通讯作者：
Tamiya, Takashi
中科院分区：
文献类型：
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作者：
Kawai, Nobuyuki;Maeda, Yukito;Tamiya, Takashi
多形性胶质母细胞瘤（GBM）的特点是组织缺氧与耐放疗和化疗。为了阐明缺氧与肿瘤诱导的新生血管形成和肿瘤侵袭性之间的生物学联系，我们分析了新诊断GBM中由F-18-氟咪唑（FMISO）PET评估的存活缺氧组织相对于Gd增强MRI中的新生血管形成和由L-甲基-C-11-蛋氨酸（MET）PET评估的肿瘤侵袭性的详细体积和空间信息。术前MET PET和Gd增强MRI。通过对MET PET上的代谢活性体积（MET摄取指数为千分之一日元1.3和千分之一日元1.5）和MRI上的Gd增强体积进行三维基于阈值的感兴趣体积（VOI）分析来计算肿瘤体积。将FMISO PET缩放到血液FMISO活性，以创建肿瘤-血液（T/B）图像。缺氧体积（HV）定义为T/B大于1.2的区域。每例患者的PET和MR图像进行配准，以分析相对于新生血管和活性肿瘤扩展的存活缺氧组织的空间位置，代谢活性肿瘤体积使用千分之一日元1.3和千分之一日元1.5的MET摄取指数定义，Gd增强体积显示出强烈的相关性（r = 0.86，p < 0.01，对于千分之一日元指数1.3; r = 0.77，p < 0.05，对于千分之一日元指数1.5）。增强体积与HV值呈显著正相关（r = 0.94，p < 0.01）。代谢活性肿瘤体积（由MET摄取指数1.3的千分之一日元定义）和HV表现出强相关性（r = 0.87，p < 0.01）。在叠加图像上，MET PET上的代谢活性区域（由MET摄取指数1.3定义）通常大于Gd增强区域，约20-30%的MET区域延伸到增强区域之外。另一方面，FMISO PET上T/B截断值为千分之一日元1.2的存活缺氧组织的表面积与Gd增强的面积没有实质性差异。体积分析表明，FMISO PET评估的存活缺氧组织与Gd增强MRI中的新生血管形成和MET PET在新诊断GBM中的肿瘤侵袭性有关。空间分析表明，代谢活跃的肿瘤可能大大低估了Gd增强MRI。补充使用MET和FMISO Gd增强MRI可能会提高对肿瘤生物学的理解，并导致最有效的肿瘤体积和治疗策略的划定。
Glioblastoma multiforme (GBM) is characterized by tissue hypoxia associated with resistance to radiotherapy and chemotherapy. To clarify the biological link between hypoxia and tumour-induced neovascularization and tumour aggressiveness, we analysed detailed volumetric and spatial information of viable hypoxic tissue assessed by F-18-fluoromisonidazole (FMISO) PET relative to neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl-C-11-methionine (MET) PET in newly diagnosed GBMs.Ten patients with newly diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI before surgery. Tumour volumes were calculated by performing a three-dimensional threshold-based volume of interest (VOI) analysis for metabolically active volume on MET PET (MET uptake indices of a parts per thousand yen1.3 and a parts per thousand yen1.5) and Gd-enhanced volume on MRI. FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B) images. The hypoxic volume (HV) was defined as the region with T/B greater than 1.2. PET and MR images of each patient were coregistered to analyse the spatial location of viable hypoxic tissue relative to neovascularization and active tumour extension.Metabolically active tumour volumes defined using MET uptake indices of a parts per thousand yen1.3 and a parts per thousand yen1.5 and the volumes of Gd enhancement showed a strong correlation (r = 0.86, p < 0.01 for an index of a parts per thousand yen1.3 and r = 0.77, p < 0.05 for an index of a parts per thousand yen1.5). The HVs were also excellently correlated with the volumes of Gd enhancement (r = 0.94, p < 0.01). The metabolically active tumour volumes as defined by a MET uptake index of a parts per thousand yen1.3 and the HVs exhibited a strong correlation (r = 0.87, p < 0.01). On superimposed images, the metabolically active area on MET PET defined by a MET uptake index of a parts per thousand yen1.3 was usually larger than the area of the Gd enhancement and about 20-30% of the MET area extended outside the area of the enhancement. On the other hand, the surface area of viable hypoxic tissue with a T/B cutoff of a parts per thousand yen1.2 on FMISO PET did not substantially differ from the area of the Gd enhancement.The volumetric analysis demonstrates that the viable hypoxic tissue assessed by FMISO PET is related to the neovascularization in Gd-enhanced MRI and the tumour aggressiveness by MET PET in newly diagnosed GBMs. The spatial analysis shows that the metabolically active tumour may be substantially underestimated by Gd-enhanced MRI. Complementary use of MET and FMISO to Gd-enhanced MRI may improve the understanding of tumour biology and lead to the most efficient delineation of tumour volume and treatment strategy.