Visualization of P2X7 Receptors in Living Human Gliomas: an 18F-GSK1482160 PET Imaging and Neuropatholopy Study.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Weiyan Zhou, Qi Yue, Yifan Yuan, Qi Huang, Kun He, Tao Hua, Junbin Han, Yingfang He, Yihui Guan, Liang Chen, Fang Xie, Ying Mao

TLDR

  • The study demonstrates the potential of P2X7R-PET imaging with 18F-GSK1482160 to characterize tumor heterogeneity and cellular composition of the microenvironment in glioma patients.
  • The two tracers show distinct spatial distribution and are associated with tumor grade and lesion contrast-enhancement status.

Abstract

PET imaging targeting the purinergic receptor subtype 7 (P2X7R) is of high interest for assessing glioma microenvironment. No reports were published regarding the P2X7R imaging in gliomas. Therefore, we compared the uptake characteristics of 18F-GSK1482160, a novel P2X7R ligand, to conventional 11C-MET PET and contrast-enhanced MRI in patients with gliomas. Thirteen glioma patients (8 grade II, 5 grade III/IV) at initial diagnosis were consecutively included and underwent 18F-GSK1482160 PET, 11C-MET PET and MRI. The semi-quantitative 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 (BPND) for the lesions. The tumor tissue was quantitatively assessed for P2X7R expression and infiltration of glioma associated microglia/macrophages (GAMs). The multilinear reference tissue model (MRTM) was sufficient for quantifying 18F-GSK1482160. The SUVRmean for duration of 50-70min correlated best to mean BPND 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-wildtype gilomas tended to have higher tracer uptake for both tracers without reaching the level of significance. P2X7R in gliomas was expressed predominately by GAMs, and its expression exhibited positive correlation with uptake of 18F-GSK1482160 (r=0.7783, p=0.0029) in the tumors. The first-in-man study of P2X7R-PET demonstrated PET with 18F-GSK1482160 and 11C-MET provides complementary information characterizing tumor heterogeneity and the cellular composition of the microenvironment in untreated gliomas.

Overview

  • The study aimed to compare the uptake characteristics of 18F-GSK1482160, a P2X7R ligand, with conventional 11C-MET PET and contrast-enhanced MRI in patients with gliomas.
  • Thirteen glioma patients underwent 18F-GSK1482160 PET, 11C-MET PET, and MRI at initial diagnosis.
  • The primary objective was to assess the P2X7R imaging in gliomas and its potential for characterizing tumor heterogeneity and cellular composition of the microenvironment.

Comparative Analysis & Findings

  • The study observed a strong linear relationship between the uptakes of 18F-GSK1482160 and 11C-MET, suggesting similar mechanisms of uptake and retention.
  • The two tracers showed distinct spatial distribution by metabolic volume comparison, but were both associated with tumor grade and lesion contrast-enhancement status.
  • IDH-wildtype gliomas tended to have higher tracer uptake for both tracers, but the difference was not statistically significant.

Implications and Future Directions

  • The study demonstrates the potential of P2X7R-PET imaging with 18F-GSK1482160 to provide complementary information about tumor heterogeneity and cellular composition of the microenvironment.
  • Future studies could investigate the serial changes in P2X7R expression and its relationship to treatment response in glioma patients.
  • The use of P2X7R-PET imaging in concert with other molecular imaging biomarkers may improve diagnostic accuracy and treatment outcomes in glioma patients.
Read Full Article