Other (O2)
Targetting folate receptor-β expressing macrophages by 18F-labelled folate PET radiotracer in rat model of myocardial infarction
List of Authors: Iqbal I, Liljenbäck H, Andriana P, Ståhle M, Virta J, Herre EA, Miner MWG, Srinivasarao M, Low PS, Knuuti J, Li XG, Roivainen A, Saraste A
Conference name: Annual Congress of the European association of nuclear Medicine
Publication year: 2022
Journal: European Journal of Nuclear Medicine and Molecular Imaging
Book title *: EANM'22
Number in series: (suppl 1)
Volume number: 49
ISSN: 1619-7070
DOI: http://dx.doi.org/10.1007/s00259-022-05924-4
URL: https://link.springer.com/article/10.1007/s00259-022-05924-4
Aim/Introduction: After myocardial infarction (MI), local inflammatory response contributes to the repair of myocardial injury. Folate receptor-β (FR-β) is expressed on the activated macrophages at the site of inflammation. In this study, we evaluated whether FR- β-targeting positron emission tomography (PET) tracer aluminum 18F-labeled NOTA-folate (18F-FOL) can be used for the detection of inflammation after MI.
Materials and Methods: We studied male Sprague-Dawley rats, 3 days and 7 days after permanent occlusion of the left coronary artery (LCA) (n = 5 and n = 4, respectively) or after sham-operation (n = 5 and n = 5, respectively). The rats were PET imaged with glucose-analog 18F-FDG for anatomical reference 24 hours before the PET imaging with 50 ± 5 MBq of 18F-FOL. Left ventricle (LV) was frozen and cut into short-axis cryosections for digital autoradiography and histology. The sections were stained with H&E for general histology and CD68 antibody for macrophages.
Results: Histology confirmed the presence of MI in 5 rats at 3 days and 4 rats at 7 days after LCA occlusion. Time-activity curves showed rapid clearance of 18F-FOL from the blood pool and stable uptake in the myocardium 20 minutes post-injection. PET images showed high focal 18F-FOL uptake co-localizing with the infarcted myocardium in all rats with MI, whereas there was no uptake in non-infarcted myocardium or myocardium of sham-operated rats. Compared to sham-operated rats, the average 18F-FOL uptake was three folds higher in the infarcted area (p = 0.01) on day 3 and two folds higher on day 7 (p = 0.03) after MI. Ex-vivo autoradiography confirmed increased 18F-FOL uptake co-localizing with the CD68- positive macrophages in the infarcted area.
Conclusion: 18F-FOL PET shows increased uptake in the infarcted myocardium in a rat model of MI. These results suggest that FR-β targeting18F-FOL PET is useful for the detection of activated macrophages after MI and may be useful for monitoring inflammatory activity in the heart after myocardial injury.