ImmunoPET imaging of TIGIT in the glioma microenvironment

Area of Science:

• Neuro-oncology
• Immunotherapy
• Molecular Imaging

Background:

• Glioblastoma (GBM) remains a challenging primary brain tumor with limited effective treatments.
• Immune checkpoint inhibitors (ICIs) show promise in other cancers but have yielded poor outcomes in GBM.
• TIGIT is an immune checkpoint receptor involved in T-cell and NK cell suppression, potentially serving as a therapeutic target and biomarker in GBM.

Purpose of the Study:

• To develop and evaluate a novel molecular imaging agent, [89Zr]Zr-DFO-anti-TIGIT, for visualizing TIGIT expression in preclinical glioblastoma models using immunoPET.
• To assess the specificity and tumor uptake of the [89Zr]Zr-DFO-anti-TIGIT tracer in the GBM tumor microenvironment.

Main Methods:

• Construction of a zirconium-89 labeled anti-TIGIT antibody ([89Zr]Zr-DFO-anti-TIGIT) for immunoPET imaging.
• Administration of the tracer to mice bearing GBM tumors.
• PET imaging and biodistribution studies to quantify tracer uptake in tumors.
• Specificity assessment using blocking antibody and irrelevant antibody control studies.

Main Results:

• [89Zr]Zr-DFO-anti-TIGIT demonstrated uptake within the tumor microenvironment of GBM-bearing mice.
• Specificity of the tracer for TIGIT was confirmed through blocking and control studies, particularly at later time points.
• The magnitude of [89Zr]Zr-DFO-anti-TIGIT uptake in tumors relative to an IgG control tracer was minimal.

Conclusions:

• The developed [89Zr]Zr-DFO-anti-TIGIT tracer shows potential for visualizing TIGIT in preclinical GBM models.
• The study highlights both the capabilities and limitations of this agent, particularly concerning the magnitude of tumor uptake.
• Further optimization may be needed for effective preclinical TIGIT-targeted immunoPET imaging in GBM.