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

TL;DR

This study compares two PET tracers for detecting heart inflammation in rats with autoimmune myocarditis, finding both effective at targeting macrophages.

Contribution

The novel contribution is evaluating [18F]SFB-FOL as a new PET tracer for myocardial inflammation and comparing it to [18F]FOL in an animal model.

Findings

Both [18F]SFB-FOL and [18F]FOL showed significantly higher uptake in inflamed myocardium compared to remote areas.

Lesion-to-remote uptake ratios were higher for [18F]SFB-FOL (5.7 ± 1.8) than [18F]FOL (3.8 ± 0.5).

No significant differences in tracer uptake or macrophage density were observed between Days 21 and 28 post-immunization.

Abstract

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.

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