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

Abstract

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. 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. 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). 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.