Tateishi K, Tateishi U, Nakanowatari S, Ohtake M, Minamimoto R, Suenaga J, Murata H, Kubota K, Inoue T, Kawahara N
From the Departments of Neurosurgery (K.T., S.N., M.O., J.S., H.M., N.K.).
AJNR Am J Neuroradiol. 2014 Feb;35(2):278-84. doi: 10.3174/ajnr.A3679. Epub 2013 Aug 8.
(62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) was developed as a hypoxic radiotracer in PET. We compared imaging features among MR imaging and (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET, FDG-PET, and L-methyl-[(11)C]methionine)-PET in gliomas.
We enrolled 23 patients who underwent (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET and FDG-PET and 19 (82.6%) who underwent L-methyl-[(11)C]methionine)-PET, with all 23 patients undergoing surgery and their diagnosis being then confirmed by histologic examination as a glioma. Semiquantitative and volumetric analysis were used for the comparison.
There were 10 newly diagnosed glioblastoma multiforme and 13 nonglioblastoma multiforme (grades II and III), including 4 recurrences without any adjuvant treatment. The maximum standardized uptake value and tumor/background ratios of (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone), as well as L-methyl-[(11)C]methionine, were significantly higher in glioblastoma multiforme than in nonglioblastoma multiforme (P = .03 and P = .03, respectively); no significant differences were observed on FDG. At a tumor/background ratio cutoff threshold of 1.9, (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) was most predictive of glioblastoma multiforme, with 90.0% sensitivity and 76.9% specificity. The positive and negative predictive values, respectively, for glioblastoma multiforme were 75.0% and 85.7% on (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone), 83.3% and 60.0% on L-methyl-[(11)C]methionine, and 72.7% and 75.0% on MR imaging. In glioblastoma multiforme, volumetric analysis demonstrated that (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) uptake had significant correlations with FDG (r = 0.68, P = .03) and L-methyl-[(11)C]methionine (r = 0.87, P = .03). However, the (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-active region was heterogeneously distributed in 50.0% (5/10) of FDG-active and 0% (0/6) of L-methyl-[(11)C]methionine)-active regions.
(62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) may be a practical radiotracer in the prediction of glioblastoma multiforme. In addition to FDG-PET, L-methyl-[(11)C]methionine)-PET, and MR imaging, (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET may provide intratumoral hypoxic information useful in establishing targeted therapeutic strategies for patients with glioblastoma multiforme.
双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)被开发用作正电子发射断层扫描(PET)中的一种乏氧放射性示踪剂。我们比较了磁共振成像(MR成像)、双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)-PET、氟代脱氧葡萄糖(FDG)-PET和L-甲基-[(11)C]蛋氨酸-PET在胶质瘤中的成像特征。
我们纳入了23例行双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)-PET和FDG-PET检查的患者,以及19例(82.6%)行L-甲基-[(11)C]蛋氨酸-PET检查的患者,所有23例患者均接受了手术,术后经组织学检查确诊为胶质瘤。采用半定量和体积分析进行比较。
有10例新诊断的多形性胶质母细胞瘤和13例非多形性胶质母细胞瘤(Ⅱ级和Ⅲ级),其中4例复发且未接受任何辅助治疗。多形性胶质母细胞瘤中双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)以及L-甲基-[(11)C]蛋氨酸的最大标准化摄取值和肿瘤/本底比值显著高于非多形性胶质母细胞瘤(分别为P = 0.03和P = 0.03);FDG检查未观察到显著差异。在肿瘤/本底比值截断阈值为1.9时,双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)对多形性胶质母细胞瘤的预测性最强,敏感性为90.0%,特异性为76.9%。双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)对多形性胶质母细胞瘤的阳性预测值和阴性预测值分别为75.0%和85.7%,L-甲基-[(11)C]蛋氨酸分别为83.3%和60.0%,MR成像分别为72.7%和75.0%。在多形性胶质母细胞瘤中,体积分析显示双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)摄取与FDG(r = 0.68,P = 0.03)和L-甲基-[(11)C]蛋氨酸(r = 0.87,P = 0.03)有显著相关性。然而,双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)活性区域在50.0%(5/10)的FDG活性区域和0%(0/6)的L-甲基-[(11)C]蛋氨酸活性区域中呈异质性分布。
双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)可能是预测多形性胶质母细胞瘤的一种实用放射性示踪剂。除了FDG-PET、L-甲基-[(11)C]蛋氨酸-PET和MR成像外,双乙酰双(N(4)-甲基硫代半卡巴腙)铜(62)-PET可能提供肿瘤内乏氧信息,有助于为多形性胶质母细胞瘤患者制定靶向治疗策略。