TY - JOUR
T1 - Folate Receptor β-Targeted PET Imaging of Macrophages in Autoimmune Myocarditis
AU - Jahandideh, Arghavan
AU - Uotila, Sauli
AU - Ståhle, Mia
AU - Virta, Jenni
AU - Li, Xiang Guo
AU - Kytö, Ville
AU - Marjamäki, Päivi
AU - Liljenbäck, Heidi
AU - Taimen, Pekka
AU - Oikonen, Vesa
AU - Lehtonen, Jukka
AU - Mäyränpää, Mikko I.
AU - Chen, Qingshou
AU - Low, Philip S.
AU - Knuuti, Juhani
AU - Roivainen, Anne
AU - Saraste, Antti
N1 - Publisher Copyright:
COPYRIGHT © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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 (SUV
mean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUV
mean, 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.
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 (SUV
mean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUV
mean, 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.
KW - Experimental autoimmune myocarditis
KW - Folate receptor
KW - Myocarditis
KW - PET
KW - Heterocyclic Compounds, 1-Ring/pharmacokinetics
KW - Humans
KW - Macrophages/metabolism
KW - Rats, Inbred Lew
KW - Rats
KW - Male
KW - Sarcoidosis/metabolism
KW - Animals
KW - Radiopharmaceuticals/pharmacokinetics
KW - Fluorine Radioisotopes/pharmacokinetics
KW - Myocarditis/diagnostic imaging
KW - Positron-Emission Tomography/methods
KW - Autoimmune Diseases/diagnostic imaging
KW - Folate Receptor 2/metabolism
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UR - http://www.scopus.com/inward/citedby.url?scp=85089400002&partnerID=8YFLogxK
U2 - 10.2967/jnumed.119.241356
DO - 10.2967/jnumed.119.241356
M3 - Article
C2 - 32284397
AN - SCOPUS:85089400002
SN - 0161-5505
VL - 61
SP - 1643
EP - 1649
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -