11C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: A stereotactic image-histology comparison

11C-methionine positron emission tomography (11C-methionine PET) provides accurate detection of brain tumors. Several reports have analyzed the correlation between uptake of 11C-methionine and Ki-67 index or microvessel density non-stereotactically and suggested that 11C-methionine uptake reflects both proliferation potential and angiogenic capability in gliomas. As gliomas possess heterogeneous histological architecture, non-stereotactic comparison of the histology and 11C-methionine PET image may not be accurate. In the present study, the correlation between 11C-methionine uptake and cell or microvessel density was analyzed using histological specimens obtained by stereotactic biopsy, and an exact local comparison of 11C-methionine PET image and histological specimens was conducted. The tumor/normal tissue (T/N) ratio of 11C-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 11C-methionine level while microvessel density was not. These results suggest that cell density contributes more to 11C-methionine uptake than microvessel density in glioma tissues and that the previously reported correlation of 11C-methionine uptake and microvessel density in glioma patients requires reevaluation.