Methyl-l-11C-Methionine PET as a Diagnostic Marker for Malignant Progression in Patients with Glioma

Abstract

Methyl-L-(11)C-methionine ((11)C-MET) PET has been shown to detect brain tumors with a high sensitivity and specificity. In this study, we investigated the potential of (11)C-MET PET to noninvasively detect tumor progression in patients with gliomas. Moreover, we analyzed the relationship between changes in (11)C-MET uptake on PET and changes in various molecular immunohistochemical markers during progression of gliomas. Twenty-four patients with histologically proven glioma were investigated repeatedly with (11)C-MET PET. (11)C-MET uptake was determined for a circular region of interest. Histologic and molecular analyses for tumor progression were performed after open surgery and stereotactic biopsy, respectively. In patients with malignant progression, the mean increase in (11)C-MET uptake was 54.4% (SD, 45.5%; range, 3.1%-162.2%), whereas in patients without a change in tumor grade, mean (11)C-MET uptake did not significantly change (3.9%; SD, 13.7%; range, -24.4% to 26.3%). The difference in the change in (11)C-MET uptake between the group with malignant progression and the group without malignant progression was highly significant (P < 0.001). Receiver-operating-curve analysis revealed a sensitivity of 90% and a specificity of 92.3% for the detection of malignant transformation by an increase in (11)C-MET uptake of more than 14.6%. Increased (11)C-MET uptake of more than 14.6% was indicative of malignant progression in all but 3 leave-one-out iterations. A detailed immunohistochemical analysis demonstrated a significant correlation between changes in (11)C-MET uptake and the expression of vascular endothelial growth factor. These data suggest that (11)C-MET-PET represents a noninvasive method to detect malignant progression in patients with gliomas. Moreover, the increase in (11)C-MET uptake during malignant progression is reflected by an increase in angiogenesis-promoting markers as vascular endothelial growth factor.