Molecular imaging of fibroblast activity after acute myocardial infarct using 99mTc-iFAP: Comparison with cardiac magnetic resonance, myocardial perfusion imaging and invasive coronary angiography.

Introduction: Cardiac remodeling is a major factor in the prognosis of patients that undergo an acute myocardial infarction (AMI). Activation of fibroblast is mandatory for repair and regeneration after AMI. Small molecules targeting fibroblast activation protein (FAP) visualized by molecular imaging has gained considerable interest in oncological community, also, FAP-specific positron emission tomography (PET) radiotracers showed promising results that warrant further research in non-malignant diseases, especially in cardiac imaging; Unfortunately, PET is not always widely available nor cost-effective in emerging countries. The objective of this pilot study is to evaluate the feasibility of imaging activated fibroblast using ^99mTc-iFAP cardiac SPECT and evaluate the uptake pattern in patients with AMI and its correlation with myocardial perfusion imaging (MPI), cardiac magnetic resonance (CMR) and invasive coronary angiography.

Methods: Prospective controlled study, twelve patients underwent cardiac ^99mTc-iFAP SPECT, myocardial perfusion imaging (MPI) at rest with ^99mTc-sestamibi, cardiac magnetic resonance (CMR), and invasive coronary angiography within 14 days after acute myocardial infarction. Myocardial FAP activity was analyzed for extent and intensity using Cedars Sinai QPS-QGS and correlated with multimodal imaging (MPI, late gadolinium enhancement and T2WI). Cardiac function was assessed at 3 months after AMI by echocardiography and correlated with FAP activity.

Results: A total of 12 patients (9 male, 3 female), culprit vessel responsible for the infarction was anterior descending coronary artery in 9 patients (75%), right coronary artery in 2 patients (16.7%) and circumflex artery in 1 patient (8.3%). Localized ^99mTc-iFAP uptake according to the affected coronary territory detected by invasive coronary angiography correlated in 12/12 patients (100%). The iFAP concentration was higher in the infarct region than in the remote zone and the extent exceeded the perfusion defect, fibrosis and extracellular edema visualized by CMR (p < 0.05). In the follow up of ventricular function at 3 months, a correlation was obtained between the intensity of iFAP uptake and left ventricular disfunction in eleven patients (p= 0.0321).

Conclusions: Myocardial uptake with ^99mTc-iFAP after AMI provided new insights into the regional pattern of fibroblast activity and its potential use in the assessment of subsequent left ventricular dysfunction. The uptake area of ^99mTc-iFAP exceeded the area of extracellular edema, this suggests that molecular imaging targeting FAP could present different phenotypic characteristics than those derived from CMR/MPI and could be complementary. These advantages make it a potential technique in the evaluation of the myocardial remodeling after AMI and a favorable method to analyze therapies directed to activated fibroblasts in order to prevent remodeling and subsequent heart failure.

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