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Targeting Macrophage Folate Receptor-β for Diagnosis and Treatment of Autoimmune Myocarditis

Created on 04 Nov 2025

Authors

Jahandideh, A., Atencio Herre, E., Nammas, W., Virta, J., Liljenback, H., Ponkamo, J., Putri, A., Zhuang, X., Rajander, J., Srinivasarao, M., Low, P. S., Lu, Y., Li, X.-G., Knuuti, J., Roivainen, A., Saraste, A.

Abstract

We investigated folate receptor-beta (FR-beta) expressed on activated macrophages as a therapeutic and imaging target in autoimmune myocarditis (AIM). Treatment with a folate-aminopterin conjugate (EC2319) targeting FR-beta-positive macrophages significantly reduced macrophage infiltration compared to saline in rat experimental AIM (P < 0.001). After immunization, FR-beta; targeting positron emission tomography (PET) tracer [18F]FOL detected myocardial inflammatory lesions and revealed reduction in inflammation following EC2319 treatment relative to saline or tumor necrosis factor-alpha inhibitor Etanercept (P < 0.001). [18F]FOL PET signal correlated with myocardial CD68-positive macrophage content (r = 0.720, P < 0.001). These findings demonstrate that EC2319 attenuates myocardial inflammation in AIM and underscore the pathogenic role of FR-beta-positive macrophages. [18F]FOL PET provides a noninvasive means of detecting myocardial inflammatory activity and therapeutic response.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 04 Nov 2025.

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