11C-PD153035, a potent and specific ATP-competitive tyrosine kinase inhibitor (TKI) of the EGF receptor, has been developed for PET imaging of epidermal growth factor receptor (EGFR) in lung cancer. The objective of the present study was to investigate the relationship of the accumulation of 11C-PD153035 and the EGFR expression level in human gliomas and to explore whether 11C-PD153035 can be used in the molecular imaging of glioma with EGFR overexpression. Eleven patients with histopathologically proven gliomas underwent 11C-PD153035 PET/CT examination before surgery. Combining MRI with the 11C-PD153035 PET/CT image, 2 specimens from different C-PD153035 uptake regions of each tumor and adjacent normal brain tissue were selected as the biopsy targets through the stereotactic technique. The radioactivity concentrations were analyzed as the mathematical maximum standardized uptake value (SUVmax) in region of interest (ROI). The EGFR expression in the biopsied tissues was analyzed by immunohistochemical staining (IHC) and western blotting. The SUVmax/WM (11C-PD153035 uptake in the white matter of the contralateral normal hemisphere) ratio was used to indicate the EGFR expression level in the ROI in PET/CT, and it was correlated with the EGFR expression detected by IHC and western blot analysis. The results demonstrated that 6 of the 8 patients with glioblastoma (GBM) were obviously visualized by 11C-PD153035 PET/CT, whereas 2 patients with GBM, 1 with anaplastic astrocytoma, and 2 with oligodendroglioma did not show significant 11C-PD153035 uptake. There were positive correlations between the SUVmax/WM and the results of IHC (r = 0.955, P < 0.01) and western blotting(r = 0.889, P < 0.010). Our preliminary findings suggest that 11C-PD153035 PET/CT is a promising method for the EGFR-targeted molecular imaging of human GBM, which may be translated into the clinic to select the appropriate population of patients for EGFR-targeted therapy and to assess the early targeted therapeutic response of malignant gliomas.