Utilizing PET Imaging To Visualize Immune Activation and Tumor Apoptosis

Area of Science:

• Oncology
• Immunology
• Radiochemistry

Background:

• Immunotherapy effectiveness relies on tumor apoptosis and immune activation.
• Noninvasive methods are needed to monitor these processes during treatment.

Purpose of the Study:

• To explore Positron Emission Tomography (PET) imaging for visualizing immune activation and tumor apoptosis.
• To target granzyme-B and caspase-3 using novel radiotracers for PET imaging.

Main Methods:

• Bioinformatic analysis of granzyme-B and caspase-3 expression.
• Development and use of [⁶⁸Ga]Ga-GZP and [⁶⁸Ga]Ga-AC3 PET tracers.
• In vivo PET/CT imaging in CT26 xenograft models treated with PD-1 inhibitor.

Main Results:

• Increased tumor uptake of both PET tracers in immunotherapy-treated mice.
• Upregulated granzyme-B and caspase-3 expression confirmed by immunofluorescence.
• Enhanced T-cell infiltration and effector molecule levels observed in treated tumors.

Conclusions:

• Granzyme-B and caspase-3 PET/CT can noninvasively visualize early immunotherapy-induced CD8+ T cell activation and tumor apoptosis.
• These PET imaging techniques offer potential for accurate immunotherapy efficacy evaluation in clinical settings.