IFN-γ PET imaging stratifies and predicts response to CD137 agonism in a syngeneic colorectal tumor model

Area of Science:

• Oncology
• Immunology
• Radiochemistry

Background:

• Interferon-γ (IFN-γ) secretion indicates an active antitumor immune response during cancer immunotherapy.
• Early prediction of treatment responders versus non-responders is a critical clinical need.
• Positron emission tomography (PET) imaging of IFN-γ may offer a solution for early response assessment.

Purpose of the Study:

• To evaluate the potential of IFN-γ PET imaging to predict immunotherapy response in a preclinical cancer model.
• To determine if IFN-γ PET can differentiate between treated responders (TR) and treated non-responders (TNR) early in treatment.

Main Methods:

• Developed and tested [⁸⁹Zr]Zr-DFO-anti-IFN-γ for PET imaging of IFN-γ.
• Administered the tracer to mice with CT26 tumors, treated with a CD137 agonist or untreated.
• Correlated tracer uptake with IFN-γ levels, tumor growth, and survival outcomes.

Main Results:

• [⁸⁹Zr]Zr-DFO-anti-IFN-γ uptake strongly correlated with intratumoral IFN-γ levels.
• PET imaging successfully stratified treated responders from non-responders, with higher uptake indicating tumor regression.
• Increased tracer uptake (>13.9 %ID/mL) was significantly associated with improved overall survival.

Conclusions:

• IFN-γ PET imaging can stratify tumor response to immunotherapy early, before morphological changes are visible.
• IFN-γ PET serves as a promising predictive biomarker for immunotherapy response.
• This imaging technique addresses the unmet clinical need for early detection of antitumor immunity.