ImmunoPET imaging of TIGIT in the glioma microenvironment

Sci Rep. 2024 Mar 4;14(1):5305. doi: 10.1038/s41598-024-55296-y.


Glioblastoma (GBM) is the most common primary malignant brain tumor. Currently, there are few effective treatment options for GBM beyond surgery and chemo-radiation, and even with these interventions, median patient survival remains poor. While immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy against non-central nervous system cancers, ICI trials for GBM have typically had poor outcomes. TIGIT is an immune checkpoint receptor that is expressed on activated T-cells and has a role in the suppression of T-cell and Natural Killer (NK) cell function. As TIGIT expression is reported as both prognostic and a biomarker for anti-TIGIT therapy, we constructed a molecular imaging agent, [89Zr]Zr-DFO-anti-TIGIT (89Zr-αTIGIT), to visualize TIGIT in preclinical GBM by immunoPET imaging. PET imaging and biodistribution analysis of 89Zr-αTIGIT demonstrated uptake in the tumor microenvironment of GBM-bearing mice. Blocking antibody and irrelevant antibody tracer studies demonstrated specificity of 89Zr-αTIGIT with significance at a late time point post-tracer injection. However, the magnitude of 89Zr-αTIGIT uptake in tumor, relative to the IgG tracer was minimal. These findings highlight the features and limitations of using 89Zr-αTIGIT to visualize TIGIT in the GBM microenvironment.

Keywords: Brain tumor; Glioma; Immunosuppression; Immunotherapy; TIGIT.

MeSH terms

  • Animals
  • Glioblastoma* / diagnostic imaging
  • Glioma* / diagnostic imaging
  • Humans
  • Mice
  • Positron-Emission Tomography
  • Receptors, Immunologic
  • Tissue Distribution
  • Tumor Microenvironment


  • Receptors, Immunologic
  • TIGIT protein, human