11C-methionine (MET) and 18F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Tetsuhiro Hatakeyama, Nobuyuki Kawai, Yoshihiro Nishiyama, Yuka Yamamoto, Yasuhiro Sasakawa, Tomotsugu Ichikawa, Takashi Tamiya
European Journal of Nuclear Medicine and Molecular Imaging 2008, 35 (11): 2009-17

PURPOSE: The purpose of this prospective study was to clarify the individual and combined role of L-methyl-(11)C-methionine-positron emission tomography (MET-PET) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades.

MATERIALS AND METHODS: Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV(max)), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining.

RESULTS: On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV(max) and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV(max) and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV(max) and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV(max) and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV(max) of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01).

CONCLUSIONS: PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.

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