Imran Iqbal, Heidi Liljenbäck, Putri Andriana, Mia Ståhle, Jenni Virta, Erika Atencio Herre, Maxwell W. G. Miner, Arman Anand, Aino Suni, Wail Nammas, Ville Kytö, Hasan Mansour A Mansour, Nathan A. Cleveland, Xiang-Guo Li, Madduri Srinivasarao, Philip S. Low, Juhani Knuuti, Anne Roivainen, Antti Saraste
Folate receptor ß (FR-ß) is expressed on activated macrophages in inflammatory conditions. In order to study FR-ß in inflammatory response following myocardial infarction (MI), we evaluated FR-ß-targeted PET imaging using aluminum fluoride-18-labeled NOTA-folate ([ 18 F]FOL) in a rat model of MI. Rats underwent [ 18 F]FOL PET imaging on 3, 7, 15, and 90 days after induction of MI by permanent coronary artery ligation or sham-operation. [ 18 F]FDG PET was performed a day before [ 18 F]FOL scan to localize the infarct area. A subset of rats underwent [ 18 F]FOL PET on day 7 and serial echocardiography until 90 days post-surgery. The [ 18 F]FOL uptake was significantly higher in infarct area than in the myocardium of sham-operated rats on day 3 (SUV 1.97 ± 0.17 vs. 0.74 ± 0.13), and remained higher on day 7 (SUV 1.35 ± 0.33 vs. 0.70 ± 0.16), day 15 (SUV 1.24 ± 0.20 vs. 0.59 ± 0.07), and day 90 (SUV 1.39 ± 0.25 vs. 0.69 ± 0.11). Autoradiography of tissue sections confirmed tracer uptake in the infarct area, where immunofluorescence showed FR-ß in CD68-positive macrophages. Uptake of [ 18 F]FOL correlated with CD68-positive macrophage density (r = 0.669, p < 0.001) and was associated with decline in left ventricular ejection fraction between days 7 and 90 post-MI (r = -0.665, p = 0.007). [ 18 F]FOL PET detects expression of FR-β, a marker of activated macrophages after MI. FR-β expression peaks early and remains elevated up to 3 months post-MI. Early FR-β expression is associated with worsening of left ventricular systolic function. LCA ligation, Left coronary artery ligation; MI, Myocardial infarction; SUV, Standard uptake values; ΔEF, Change in ejection fraction. Created with BioRender.com .