Cardiac fibrosis can contribute to heart failure, a major cause of death after a heart attack. Credit: Shutterstock

Research from the Society of Nuclear Medicine and Molecular Imaging indicates that a new form of positron emission tomography (PET) scanning can effectively image fibroblast activation after a heart attack.

Fibroblasts play an important role in preserving the structural integrity of the heart after an attack, but excessive cardiac fibrosis can lead to increased left ventricle stiffness and decreased cardiac contraction. This can contribute to heart failure, a major cause of death after a heart attack.

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The researchers sought to evaluate the feasibility of imaging activated fibroblasts after heart attack using a novel 68Ga-FAPI-04 PET fibroblast activation protein inhibitor.

Technische Universität München research fellow Zohreh Varasteh said: “Imaging of activated fibroblasts using 68Ga-FAPI-04 PET may have significant diagnostic and prognostic value.”

The study involved 20 rats subject to a heart attack by permanent ligation of the left anterior descending coronary artery, as well as four sham-operated rats that did not undergo the ligation. 68Ga-FAPI-04 PET scans were performed at one, three, six, 14, 23 and 30 days after the heart attacks, and 18F-FDG scans were performed three days after. Dynamic 68Ga-FAPI-04 PET and blocking studies were performed on the rats on day seven. Ex vivo imaging, autoradiography, histologic studies and immunofluorescence staining were also conducted to validate results of in vivo imaging.

Researchers found that uptake of 68Ga-FAPI-04 PET peaked six days after ligation and decreased rapidly to the background level by two weeks after the heart attack. Uptake accumulated mainly at the border of the infarcted myocardium, with high contrast and minimal uptake in normal myocardium. The exact location of the 68Ga-FAPI-04 uptake was confirmed by ex vivo imaging, as well as autoradiography and histologic findings.

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Varasteh said: “While preclinical development of potential anti-fibrotic approaches is far advanced, there has been little clinical validation due to the lack of sensitive and specific imaging technologies for assessing cardiac fibrosis progression or regression. In this regard, 68Ga-FAPI-04 PET has emerged as an important tool for the detection of fibrotic processes in the efforts to improve heart failure therapy.

“In the future, these advances in imaging may also be applied to other conditions associated with the activation of fibroblasts, such as hypertension, ischemic, dilated and hypertrophic cardiomyopathies, cancer therapy-related cardiotoxicity, liver cirrhosis and pulmonary fibrosis.”