Molecular Imaging of Collagen Turnover in Myocardial Infarction

Area of Science:

• Cardiovascular Imaging
• Molecular Imaging
• Biomarker Development

Background:

• Cardiac fibrosis is a major cause of cardiomyopathy post-myocardial infarction (MI).
• Current imaging lacks sensitivity for dynamic collagen turnover, a key process in fibrosis.
• Molecular imaging of collagen denaturation could improve risk stratification and anti-fibrotic therapy development.

Purpose of the Study:

• To evaluate 99mTc-(HE)3-(GPO)9, a novel radiotracer targeting denatured collagen, as a biomarker for collagen turnover post-MI.
• To assess the feasibility of using this tracer for non-invasive imaging of cardiac fibrosis.

Main Methods:

• Induction of MI in mice, followed by SPECT/CT imaging with 99mTc-(HE)3-(GPO)9 or a control tracer.
• In vivo and ex vivo quantification of tracer uptake via gamma counting and autoradiography.
• Assessment of collagen denaturation, matrix metalloproteinase (MMP) activity, and tracer binding in human cardiac tissue.

Main Results:

• 99mTc-(HE)3-(GPO)9 showed significantly higher uptake in the infarct zone of MI mice compared to controls (P < 0.0001).
• Autoradiography confirmed SPECT findings, demonstrating a strong correlation (R = 0.81, P < 0.01).
• The tracer specifically bound to denatured collagen in both mouse and human fibrotic cardiac tissue.

Conclusions:

• 99mTc-(HE)3-(GPO)9 enables non-invasive in vivo detection of denatured collagen, a marker of fibrotic remodeling after MI.
• This radiotracer holds promise for assessing cardiac fibrosis and potentially guiding personalized cardiomyopathy management.
• Combined imaging of collagen, procollagen, and MMP activation may offer a comprehensive molecular fingerprint of cardiac fibrosis.