FAPI-Targeted Molecular Imaging: Transforming Insights into Post-Ischemic Myocardial Remodeling?

Abstract

Post-ischemic myocardial remodeling significantly impacts clinical outcomes after acute myocardial infarction (MI), involving structural and functional changes such as ventricular dilation, infarct wall thinning, and fibrosis development. These processes, driven by inflammatory cascades, neurohormonal activation, and extracellular matrix remodeling, result in impaired cardiac output and an increased risk of heart failure. Imaging with fibroblast activation protein inhibitors (FAPI) has emerged as a promising non-invasive tool for assessing myocardial fibrosis via positron emission tomography (PET) or single-photon emission computed tomography (SPECT), targeting activated fibroblasts; the mediators of reparative and fibrotic processes. This innovative approach enables precise visualization and quantification of fibrosis dynamics, surpassing traditional imaging modalities. Preclinical studies using [⁶⁸Ga]Ga-FAPI PET/computed tomography (CT) demonstrated the tracer's specificity for fibroblast activation and its peak uptake in the infarct border zone at day 6 post-MI. These findings, corroborated by histology and autoradiography, highlight its potential for tracking reparative fibrosis. Clinical translation of FAPI imaging was recently achieved with [⁶⁸Ga]Ga-FAPI-46 PET/magnetic resonance imaging (MRI), showing persistent fibroblast activity beyond infarct zones and strong correlations with myocardial injury markers. Complementary research on [^99mTc]Tc-HFAPi SPECT imaging in patients post-MI established its predictive value for left ventricular remodeling, emphasizing its cost-effectiveness and accessibility compared with PET. These advancements underscore FAPI-based imaging's potential to transform risk stratification and therapeutic guidance in post-MI care.

Fig. 1

Examples of acute myocardial infarction, imaged at 23 days (A) and 3 days (B) post-infarction, involving the anterior (A) and inferior (B) walls. Fused PET and cardiac magnetic resonance (CMR) images are shown in short-axis and 2-chamber views. Late gadolinium enhancement is visible in the anterior (A) and inferior (B) walls (blue arrows). Strong [⁶⁸Ga]FAPI-46 uptake is detected in the infarcted area and extends into the peri-infarct region. Matched polar maps illustrate increased [⁶⁸Ga]FAPI-46 signal in the anterior and inferior walls, respectively, alongside corresponding T2-weighted short-axis images. (C) TBRmax values for each myocardial segment in acute anterior infarcts are plotted over time. Bolded values in segments 7–9, 13–15, and 17 indicate statistically significant changes over time (P < 0.05). [⁶⁸Ga]FAPI-46 ⁶⁸Gallium-fibroblast activation protein inhibitor-46, CMR cardiac magnetic resonance, PET positron emission tomography, TBRmax maximal target-to-background ratio. Reprinted from [21], under a creative commons attribution 4.0 international license (http://creativecommons.Org/licenses/by/4.0/). No changes were made