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  • Folate Receptor β-Targeted PET Imaging of Macrophages in Autoimmune Myocarditis.

Folate Receptor β-Targeted PET Imaging of Macrophages in Autoimmune Myocarditis.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2020-04-15)
Arghavan Jahandideh, Sauli Uotila, Mia Ståhle, Jenni Virta, Xiang-Guo Li, Ville Kytö, Päivi Marjamäki, Heidi Liljenbäck, Pekka Taimen, Vesa Oikonen, Jukka Lehtonen, Mikko I Mäyränpää, Qingshou Chen, Philip S Low, Juhani Knuuti, Anne Roivainen, Antti Saraste
ABSTRACT

Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum 18F-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid conjugated folate (18F-FOL) is a PET tracer targeting folate receptor β (FR-β), which is expressed on activated macrophages at sites of inflammation. We evaluated 18F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied the expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund adjuvant. Control rats (n = 6) were injected with Freund adjuvant alone. 18F-FOL was intravenously injected, followed by imaging with a small-animal PET/CT scanner and autoradiography. Contrast-enhanced high-resolution CT or 18F-FDG PET images were used for coregistration. Rat tissue sections and myocardial autopsy samples from 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 of 18 immunized rats showed focal macrophage-rich inflammatory lesions, with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial 18F-FOL uptake colocalizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P < 0.01). Ex vivo autoradiography of tissue sections confirmed uptake of 18F-FOL in myocardial inflammatory lesions. Uptake of 18F-FOL in inflamed myocardium was efficiently blocked by a nonlabeled FR-β ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-β-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, 18F-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-β, which were also present in human cardiac sarcoid lesions. Imaging of FR-β expression is a potential approach for the detection of active myocardial inflammation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pertussis toxin from Bordetella pertussis, buffered aqueous glycerol solution
Sigma-Aldrich
Freund′s Adjuvant, Complete, cell suspension
Sigma-Aldrich
Myosin, Calcium activated from porcine heart, buffered aqueous glycerol solution, 0.1-0.5 units/mg protein (biuret)