Multimodal Molecular Imaging Detects Early Responses to Immune Checkpoint Blockade

Area of Science:

• Oncology
• Medical Imaging
• Biochemistry

Background:

• Immune checkpoint blockade (ICB) is a cancer therapy with inconsistent patient responses.
• Noninvasive methods to assess early ICB treatment response are lacking.

Purpose of the Study:

• To evaluate multimodal imaging, including hyperpolarized ¹³C MRI and dynamic contrast-enhanced (DCE) MRI, for noninvasive assessment of early response to ICB therapy.
• To correlate imaging biomarkers with tumor response and survival in preclinical cancer models.

Main Methods:

• Utilized hyperpolarized ¹³C MRI with [1-¹³C] pyruvate and [1,4-¹³C2] fumarate, and DCE MRI in MC38 (high ICB sensitivity) and B16-F10 (low ICB sensitivity) mouse tumor models.
• Assessed changes in tumor glycolysis, necrosis, and perfusion/permeability following dual PD-L1 and CTLA4 blockade.
• Correlated imaging biomarkers with tumor volume and survival outcomes.

Main Results:

• Glycolytic flux decreased post-treatment in less sensitive B16-F10 tumors.
• Increased necrotic cell death was observed in ICB-sensitive MC38 tumors using [1,4-¹³C2] fumarate conversion.
• DCE-MRI showed increased perfusion/permeability in MC38 tumors, with a similar trend in B16-F10 tumors.
• All imaging biomarkers correlated linearly with future survival when tumor volume was considered.

Conclusions:

• Hyperpolarized ¹³C MRI and DCE MRI show promise as noninvasive biomarkers for early detection of ICB therapy response.
• Multimodal imaging can provide insights into tumor metabolic and vascular changes during ICB treatment.
• These imaging techniques may aid in predicting patient outcomes and optimizing cancer immunotherapy strategies.