A Pilot Study on EGFR-Targeted Molecular Imaging of PET/CT With 11C-PD153035 in Human Gliomas

Abstract

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.

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“…Nonetheless, despite the high intracellular levels of ATP we were able to observe binding of [ 3 H]LRRK2-IN-1 in vivo , especially in the periphery, suggesting that the ATP-binding site is not fully saturated by ATP in vivo . Although, the endogenous ATP will largely out-compete binding of a reversible inhibitor to the ATP-binding site on the enzyme, it could be speculated that an irreversible inhibitor would be less susceptible to such competition and thus ultimately be more effective as strategy for a PET tracer for this target [56, 57]. …”

Evaluate the Feasibility of Gd-based Contrast Clearance Differenceto Delineate Subvolume Target in Primary and Metastatic Brain Tumors Radiotherapy- A Prospective Study

“…5 prompted tumor recurrence by means of studying metabolites of recurrent gliomas, but whose disadvantage was that not independent indicator for diagnosis. Functional MRI which concluded DSC-MRI and DCE-MRI could effectively evaluate vascular permeability and angiogenesis [12]. Some studies have shown that value of relative cerebral blood volume (rCBV) could be seen as one of the most valuable parameters for evaluating tumor classi cation [13].…”

Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

“…A detailed metabolic investigation in rodents was also reported [87]. More recently, preliminary data detailing the potential of [ 11 C]PD153035 for EGFR-expressing glioma imaging has been reported [88]. In that study, [ 11 C]PD153035 tracer uptake correlated to EGFR expression irrespective of the mutation status.…”