Folate Receptor ß-Targeted PET Imaging of Macrophages in Autoimmune Myocarditis.
J Nucl Med
; 61(11): 1643-1649, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32284397
ABSTRACT
Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum 18F-labeled 1,4,7-triazacyclononane-N,N',Nâ³-triacetic acid conjugated folate (18F-FOL) is a PET tracer targeting folate receptor ß (FR-ß), 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-ß 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-ß.Results:
The myocardium of 10 of 18 immunized rats showed focal macrophage-rich inflammatory lesions, with FR-ß 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-ß ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-ß-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-ß, which were also present in human cardiac sarcoid lesions. Imaging of FR-ß expression is a potential approach for the detection of active myocardial inflammation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
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Radioisótopos de Flúor
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Radiofármacos
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Tomografía de Emisión de Positrones
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Receptor 2 de Folato
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Compuestos Heterocíclicos con 1 Anillo
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Macrófagos
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Miocarditis
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Nucl Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Finlandia