62Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET in Human Gliomas: Comparative Study with [18F]Fluorodeoxyglucose and L-Methyl-[11C]Methionine PET

BACKGROUND AND PURPOSE: Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) was developed as a hypoxic radiotracer in PET. We compared imaging features among MR imaging and Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET, FDG-PET, and L-methyl-[C-11]methionine)-PET in gliomas. MATERIALS AND METHODS: We enrolled 23 patients who underwent Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET and FDG-PET and 19 (82.6%) who underwent L-methyl-[C-11]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. RESULTS: 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 Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone), as well as L-methyl-[C-11]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, Cu-62-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 Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone), 83.3% and 60.0% on L-methyl-[C-11]methionine, and 72.7% and 75.0% on MR imaging. In glioblastoma multiforme, volumetric analysis demonstrated that Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) uptake had significant correlations with FDG (r = 0.68, P = .03) and L-methyl-[C-11]methionine (r = 0.87, P = .03). However, the Cu-62-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-[C-11]methionine)-active regions. CONCLUSIONS: Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) may be a practical radiotracer in the prediction of glioblastoma multiforme. In addition to FDG-PET, L-methyl-[C-11]methionine)-PET, and MR imaging, Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET may provide intratumoral hypoxic information useful in establishing targeted therapeutic strategies for patients with glioblastoma multiforme.