Molecular Imaging of Fibroblast Activity in Radiation-Induced Acute Myocardial Damage Using a [18F]AlF-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04

Abstract

<h3>Purpose/Objective(s)</h3> A previous retrospective analysis revealed increased [¹⁸F]AlF-NOTA-FAPI uptake in myocardial tissue of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). The present study investigated and verified the feasibility of [¹⁸F]AlF-NOTA-FAPI positron emission tomography (PET)/computed tomography (CT) imaging for detecting radiation-induced myocardial damage (RIMD). <h3>Materials/Methods</h3> Myocardial FAPI uptake was analyzed before radiotherapy and during radiotherapy (36–50 Gy) in 13 ESCC patients treated with CCRT. In an animal study, a single dose of 50 Gy was delivered to the cardiac apex of female Wistar rats using conformal radiotherapy. RIMD model rats were scanned with [¹⁸F]AlF-NOTA-FAPI PET/CT weekly for 12 weeks, and then MRI was conducted. Dynamic, competition, and [¹⁸F]FDG PET/CT studies were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. <h3>Results</h3> Three patients showed potentially increased FAPI uptake in myocardial tissue after radiotherapy. In the RIMD rat model, a significant increase in FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure, with peak values observed in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardial region than in remote myocardial tissue, as identified by decreased [¹⁸F]FDG uptake and confirmed by autoradiography, Masson's trichrome staining and immunohistochemical staining. The left ventricular ejection fraction (LVEF) remained unchanged from baseline at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. <h3>Conclusion</h3> An increase in myocardial uptake of [¹⁸F]AlF-NOTA-FAPI occurred in patients with ESCC after radiotherapy. These results indicated that FAPI PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF is detected, indicating the clinical potential of FAPI as a radiotracer for in vivo imaging of RIMD.