(11)C-methionine positron emission tomography ((11)C-methionine PET) provides accurate detection of brain tumors. Several reports have analyzed the correlation between uptake of (11)C-methionine and Ki-67 index or microvessel density non-stereotactically and suggested that (11)C-methionine uptake reflects both proliferation potential and angiogenic capability in gliomas. As gliomas possess heterogeneous histological architecture, non-stereotactic comparison of the histology and (11)C-methionine PET image may not be accurate. In the present study, the correlation between (11)C-methionine uptake and cell or microvessel density was analyzed using histological specimens obtained by stereotactic biopsy, and an exact local comparison of (11)C-methionine PET image and histological specimens was conducted. The tumor/normal tissue (T/N) ratio of (11)C-methionine positron emission tomography was found to correlate better with cell density (R=0.747, p=0.000042) and Ki-67 index (R=0.675, p=0.00041) than with microvessel density (R=0.467, p=0.025) in a histological comparison using a stereotactic image. Furthermore, multiple linear regression analysis revealed that cell density was the key determinant for predicting (11)C-methionine level while microvessel density was not. These results suggest that cell density contributes more to (11)C-methionine uptake than microvessel density in glioma tissues and that the previously reported correlation of (11)C-methionine uptake and microvessel density in glioma patients requires reevaluation.
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