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Visualization of P2X7 Receptors in Living Human Gliomas: An 18F-GSK1482160 PET Imaging and Neuropathology Study
Weiyan Zhou1, Qi Yue2, Yifan Yuan3
1Huashan Hospital, Shanghai, China.
Purpose:
PET imaging targeting the purinergic receptor subtype 7 (P2X7R) is of high interest for assessing the glioma microenvironment. No reports were published with regard to the P2X7R imaging in gliomas. Therefore, we compared the uptake characteristics of 18F-GSK1482160, a novel P2X7R ligand, to conventional methyl-11C-methionine (11C-MET) PET and contrast-enhanced MRI in patients with gliomas.
Experimental Design:
Thirteen patients with glioma (8 grade II and 5 grade III/IV) at initial diagnosis were consecutively included and underwent 18F-GSK1482160 PET, 11C-MET PET, and MRI. The semiquantitative analyses were performed in both 18F-GSK1482160 and 11C-MET PET images. Dynamic 18F-GSK1482160 PET analysis (n = 8) generated parametric maps of binding potential for the lesions. The tumor tissue was quantitatively assessed for P2X7R expression and infiltration of glioma-associated microglia/macrophages.
Results:
The multilinear reference tissue model was sufficient for quantifying 18F-GSK1482160. The mean standardized uptake value ratio for the duration of 50 to 70 minutes correlated best with mean binding potential in the dynamic scan analysis. A strong linear relationship between the uptakes of 18F-GSK1482160 and 11C-MET was observed. The two tracers showed distinct spatial distribution by metabolic volume comparison but were both associated with tumor grade and lesion contrast-enhancement status. IDH wild-type gliomas tended to have higher tracer uptake for both tracers without reaching the level of significance. P2X7R in gliomas was expressed predominately by glioma-associated microglia/macrophages, and its expression exhibited positive correlation with uptake of 18F-GSK1482160 (r = 0.7783; P = 0.0029) in the tumors.
Conclusions:
The first-in-man study of P2X7R PET demonstrated that PET with 18F-GSK1482160 and 11C-MET provides complementary information, characterizing tumor heterogeneity and the cellular composition of the microenvironment in untreated gliomas.
