PET Imaging of Cardiac Inflammation in Viral Myocarditis Using a DPP4-Targeted Probe

Area of Science:

• Cardiovascular Imaging
• Molecular Imaging
• Immunology

Background:

• Viral myocarditis diagnosis lacks reliable non-invasive imaging.
• Dipeptidyl peptidase-4 (DPP4) is a potential biomarker for cardiac inflammation.

Purpose of the Study:

• To develop and evaluate 68Ga-DOTA-linagliptin (68Ga-linagliptin) as a novel PET probe for detecting myocarditis.
• To assess the diagnostic and potential therapeutic utility of 68Ga-linagliptin.

Main Methods:

• PET probe development targeting DPP4.
• Animal models of Coxsackievirus B3 (CVB3) induced myocarditis.
• PET/CT imaging, Western blotting, immunostaining, single-cell sequencing, and molecular simulations.

Main Results:

• Elevated cardiac DPP4 expression was observed in mice with CVB3 myocarditis, primarily on infiltrating immune cells.
• 68Ga-linagliptin demonstrated high-affinity binding to DPP4 and significant uptake in inflamed myocardium.
• PET/CT imaging accurately visualized cardiac inflammation, correlating with histological findings.

Conclusions:

• 68Ga-linagliptin enables sensitive, non-invasive visualization of cardiac inflammation in viral myocarditis.
• The probe shows potential for early diagnosis and may offer combined diagnostic and therapeutic benefits.