Comparing Two Folate Receptor β-Targeted Tracers in a Rat Model of Experimental Autoimmune Myocarditis




Atencio Herre, Erika; Li, Xiang-Guo; Liljenbäck, Heidi; Palani, Senthil; Andriana, Putri; Jahandideh, Arghavan; Virta, Jenni; Iqbal, Imran; Dillemuth, Pyry; Kunnas, Jonne; Miner, Maxwell W.G.; Rajander, Johan; Mansour A Mansour, Hasan; Cleveland, Nathan A.; Srinivasarao, Madduri; Low, Philip S.; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne

PublisherAmerican Chemical Society (ACS)

2025

ACS pharmacology & translational science

ACS Pharmacology & Translational Science

acsptsci.4c00749

2575-9108

2575-9108

DOIhttps://doi.org/10.1021/acsptsci.4c00749

https://doi.org/10.1021/acsptsci.4c00749

https://research.utu.fi/converis/portal/detail/Publication/499052197



Folate receptor β (FR-β) expression may serve as a marker of activated macrophages involved in autoimmune myocarditis. The positron emission tomography (PET) tracer N-succinimidyl 4-[18F]fluorobenzoate-conjugated folate ([18F]SFB-FOL) effectively targets FR-β-positive macrophages in rheumatoid arthritis. Here, we examined [18F]SFB-FOL for detecting myocardial inflammation via FR-β in a rat model of experimental autoimmune myocarditis (EAM), in comparison with the established FR-β-targeted PET tracer aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated folate ([18F]FOL). EAM was induced in 22 Lewis rats through cardiac myosin immunization. Rats underwent 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET to visualize myocardium, followed by dynamic PET with [18F]SFB-FOL or [18F]FOL at Days 14, 21, or 28 postimmunization. Postimaging, myocardial tissues were assessed by γ-counting, autoradiography, and CD68 immunohistochemistry to quantify macrophage presence. Both tracers showed high radiochemical purity and in vivo stability. Inflammation-rich myocardial lesions were confirmed, with macrophages occupying 9.9% ± 1.1 of the tissue area. PET imaging revealed significantly higher uptake of both tracers in inflamed myocardium versus remote areas, confirmed by histology and autoradiography. Lesion-to-remote uptake ratios were 5.7 ± 1.8 for [18F]SFB-FOL and 3.8 ± 0.5 for [18F]FOL. Blood clearance and renal excretion were rapid for both tracers. No significant differences were observed in tracer uptake or macrophage density between Days 21 and 28. [18F]SFB-FOL is a suitable tracer for detecting active myocardial inflammation via FR-β in EAM and performs comparably to [18F]FOL.


The study was supported financially by grants from the Jane and Aatos Erkko Foundation, the Sigrid Jusélius Foundation, the Finnish Foundation for Cardiovascular Research, the Research Council of Finland (#350117, #343152), and the Turku University Foundation. E.A.H. is a PhD student supported in part by the Drug Research Doctoral Programme of the University of Turku Graduate School and by the doctoral module of the InFLAMES Flagship.


Last updated on 2025-29-08 at 12:59