Mitochondrial Imaging Detects Early Cardiac Responses to Cancer Immunotherapy

Area of Science:

• Cardiology
• Oncology
• Nuclear Medicine
• Immunology

Background:

• Cancer therapies improve survival but pose significant cardiac risks.
• Conventional therapies cause cardiotoxicity via mitochondrial dysfunction; immunotherapies induce myocarditis via T cell infiltration.
• Current methods for early cardiac risk detection lack sensitivity.

Purpose of the Study:

• To evaluate [18F]F-AraG PET as an early biomarker for cardiac involvement across various cancer therapies.
• To assess the tracer's ability to image both activated T cells and cardiomyocytes.
• To establish [18F]F-AraG PET as a tool for simultaneous assessment of cardiac effects and anti-tumor immunity.

Main Methods:

• Utilized [18F]F-AraG Positron Emission Tomography (PET) imaging.
• Assessed cardiac uptake in healthy individuals across different demographics.
• Evaluated cardiac uptake patterns in cancer patients undergoing conventional therapy and immune checkpoint inhibitors.
• Correlated [18F]F-AraG uptake with electrocardiogram (ECG) abnormalities.

Main Results:

• [18F]F-AraG demonstrated clear, consistent, and uniform cardiac uptake in healthy subjects.
• Cancer patients on conventional therapy showed increased cardiac uptake.
• Patients on immune checkpoint inhibitors exhibited further increases and regional heterogeneity in uptake, suggesting T cell infiltration.
• Abnormal [18F]F-AraG cardiac uptake patterns correlated with ECG abnormalities.

Conclusions:

• [18F]F-AraG PET is a first-in-class imaging tool for early detection of cancer therapy-related cardiac effects.
• The tracer can simultaneously assess early anti-tumor immunity and cardiac involvement.
• [18F]F-AraG PET offers a sensitive method for monitoring cardiotoxicity across diverse cancer treatment modalities.