RT Journal Article
SR Electronic
T1 Folate Receptor β–Targeted PET Imaging of Macrophages in Autoimmune Myocarditis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1643
OP 1649
DO 10.2967/jnumed.119.241356
VO 61
IS 11
A1 Jahandideh, Arghavan
A1 Uotila, Sauli
A1 Ståhle, Mia
A1 Virta, Jenni
A1 Li, Xiang-Guo
A1 Kytö, Ville
A1 Marjamäki, Päivi
A1 Liljenbäck, Heidi
A1 Taimen, Pekka
A1 Oikonen, Vesa
A1 Lehtonen, Jukka
A1 Mäyränpää, Mikko I.
A1 Chen, Qingshou
A1 Low, Philip S.
A1 Knuuti, Juhani
A1 Roivainen, Anne
A1 Saraste, Antti
YR 2020
UL http://jnm.snmjournals.org/content/61/11/1643.abstract
AB 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.