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.
['Yoshiko Okita', 'Manabu Kinoshita', 'Tetsu Goto', 'Naoki Kagawa', 'Haruhiko Kishima', 'Eku Shimosegawa', 'Jun Hatazawa', 'Naoya Hashimoto', 'Toshiki Yoshimine']
(11)C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: A stereotactic image-histology comparison.