Cardiac fibroblast activation after acute myocardial infarction: pilot study using technetium 99m-iFAP SPECT

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Instituto Nacional de Investigaciones Nucleares (ININ). Background/Introduction Excessive fibrosis and persistent active fibroblasts can lead to increased left ventricular stiffness and, thus, heart failure. Cardiac remodeling is an important factor in the prognosis of patients after an acute myocardial infarction (AMI), and fibroblast activation is mandatory for repair and regeneration of the damage. There's an increasing use of molecular imaging in cardiovascular processes, such as molecules targeting fibroblast activation protein (FAP). FAP inhibitors (iFAP) radiolabeled with 68Ga in PET/CT have demonstrated adequate biodistribution and high uptake by activated fibroblasts in patients with cardiovascular risk factors and after acute myocardial infarction. Unfortunately, PET is not always widely available or cost-effective. Purpose This pilot study evaluates the feasibility of imaging activated fibroblast using 99mTc-iFAP SPECT in patients after AMI and its correlation with myocardial perfusion imaging (MPI), cardiac magnetic resonance (CMR) and invasive coronary angiography (ICA). Methods A prospective study with recent first AMI and non-previous known coronary artery disease patients were included. They underwent 99mTc-MIBI MPI SPECT and 99mTc-iFAP SPECT (including whole-body scan and thorax anterior static image acquired at 20, 60, and 120 min for the iFAP) and CMR/ICA within 14 days (+-2) after AMI. Qualitative and quantitative analysis was performed using a 17 segments model using QPS (Cedars Sinai) to determine the infarct extension from MPI and the correlation with the 99mTc-iFAP uptake pattern. A visual grading scale was established to assess localized tracer uptake and segments belonging to the hypoperfused area of the culprit's vessel. CMR yielded an area of injury with late gadolinium enhancement (LGE) and correlated with MPI studies. Results Five patients with STEMI were included (mean age of 63). Localized uptake of 99mTc-iFAP was observed in all patients with according to the affected coronary territory detected by ICA in 100% of patients (four anterior STEMI, one inferior STEMI). No radiotracer uptake was observed in the non-infarcted territories. Agreement between myocardial iFAP uptake, MIBI myocardial perfusion defect, CMR LGE, and ICA findings are presented in figure 1. An agreement of mismatch in polar maps between iFAP and MPI was performed, obtaining an excellent mismatch pattern in all patients, especially in transmural infarct segments. The best quality image was obtained at 60 minutes. Conclusions We successfully carried out the first pilot study with the patented 99mTc-iFAP molecule with SPECT technique. 99mTc-iFAP is a promising novel biomarker in assessing myocardial injury in sites where PET/CT is unavailable. There is an excellent correlation between iFAP uptake with the perfusion defect, LGE, and invasive anatomical obstruction findings. It is feasible and necessary to extend the inclusion of patients to a larger sample.