Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling
Johannes Siebermair, Miriam Köhler, Jana Kupusović, Stephan G. Nekolla, Lukas Kessler, Justin Ferdinandus, Nika Guberina, Martin Stuschke, Hong Grafe, Jens T. Siveke, Simon Kochhäuser, Wolfgang P. Fendler, Matthias Totzeck, Reza Wakili, Lale Umutlu, Thomas Schlosser, Tienush Rassaf, Christoph Rischpler
Abstract
Background Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging. Method and results Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N=32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUV max 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUV mean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUV mean uptake, the latter with a very strong correlation with remote uptake ( R 2 = .74, P < .01). Conclusion Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.