Collagen-Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis

Area of Science:

• Cardiovascular Research
• Molecular Imaging
• Biomarker Discovery

Background:

• Cardiac fibrosis, excessive extracellular matrix deposition, is a hallmark of heart disease.
• Current molecular imaging methods are limited in assessing diffuse cardiac fibrosis.
• Targeted probes for cardiac extracellular matrix could enhance diagnosis and treatment.

Purpose of the Study:

• To evaluate collagen-targeted peptides for detecting diffuse cardiac fibrosis.
• To assess the feasibility of near-infrared imaging for visualizing cardiac fibrosis in vivo and in human samples.

Main Methods:

• Development and testing of two collagen-targeting peptides (T peptide and EP-3533) labeled with near-infrared fluorophores.
• Systemic and cardiac uptake quantification using ex vivo near-infrared imaging in a mouse model and human ischemic hearts.
• Validation of peptide specificity and collagen accumulation via immunohistochemistry and co-immunostaining.

Main Results:

• Peptide accumulation correlated with increased collagen types I and IV in fibrotic mouse hearts.
• The T peptide successfully identified intermediate and severe cardiomyopathic phenotypes in mice.
• Human patient samples showed collagen-enhancement capabilities, supporting clinical translation.

Conclusions:

• Collagen-binding peptides enable molecular imaging of diffuse cardiac fibrosis.
• This approach demonstrates significant feasibility and translation potential for noninvasive cardiac fibrosis detection.