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Mitochondrial Imaging Detects Early Cardiac Responses to Cancer Immunotherapy
Abstract:
Advances in cancer therapy have improved survival but introduced substantial cardiac risk. Mitochondrial dysfunction underlies cardiotoxicity from conventional therapy, while T cell infiltration drives immunotherapy-related myocarditis. Early detection remains challenging, as current biomarkers and imaging lack sensitivity. Here, we show that [ 18 F]F-AraG, a mitochondrial PET tracer that images both activated T cells and cardiomyocytes, may provide an early biomarker of cardiac involvement across different cancer therapies. Healthy cardiac uptake was clearly detectable, consistent across age and sex, and spatially uniform. In patients with cancer, conventional therapy increased cardiac uptake, while immune checkpoint inhibitors induced further increases and regional heterogeneity suggestive of T cell infiltration. Abnormal [ 18 F]F-AraG cardiac uptake patterns were observed alongside ECG abnormalities. These findings establish [ 18 F]F-AraG PET as a first-in-class imaging tool for simultaneous assessment of early anti-tumor immunity and cancer therapy-related cardiac effects.
Insights
A novel PET tracer, [18F]F-AraG, can detect early cardiac risks from cancer therapies by imaging both immune cells and heart muscle. This tool aids in assessing cardiac effects and anti-tumor immunity simultaneously.
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.
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