Aim/Introduction:Early detection of myocarditis, which ischaracterized by inflammation of the myocardium and myocytenecrosis, is challenging due to a lack of non-invasive techniquesspecific enough to detect active inflammation. Targeting folatereceptor β (FR-β), which is expressed on activated macrophages,Al[18F]F-labeled 1,4,7,-triazacylononane-N,N’,N’’-triacetic acidconjugated folate ([18F]FOL) has shown specific uptake in FR-βpositive macrophages in inflammatory myocardial lesions [1]. Inthis study, we evaluated FR-β-targeted tracer N-succinimidyl 4-[18F]fluorobenzoate-labeled folate ([18F]SFB-FOL) for its ability to targetactive myocardial inflammation via FR-β, and compared it to [18F]FOL in an experimental myocarditis model.

Materials and Methods:Myocarditis was induced in Lewis rats (n=11) via immunizationswith porcine cardiac myosin in Freund’s complete adjuvant. Foranatomical reference, 10-min static PET were performed using[18F]FDG. Then, rats underwent 60-min dynamic PET with [18F]FOL(n=4) and [18F]SFB-FOL (n=7) at 20 and 21 days, respectively, afterimmunization. Ex vivo gamma counting of the excised tissues andautoradiography of myocardium cryosections were performedafter scans, followed by evaluation of the presence of macrophagesby CD68 immunohistochemical staining.

Results: Both [18F]SFBFOLand [18F]FOL were prepared in high radiochemical purity(98%±3 and 91%±9, respectively). [18F]SFB-FOL proved to be stableat shelf-life for up to four hours (94% purity), as well as in healthyLewis rats (85%±9 intact tracer, n=4) after one hour. Myocardiumof immunized rats showed macrophage-rich inflammatory lesionsand had an average area of 10%±1 (n=6) CD68-positive cells. An invivo head-to-head comparison showed both tracers were rapidlycleared from blood circulation, excreted through kidneys to theurine, and showed a higher SUV in inflamed lesions than in theremote myocardium and blood pool from 10-60 min of PET imaging.Despite [18F]FOL tended to have higher lesion uptake, there wasno significant difference in the lesion-to-remote uptake ratiosbetween the tracers. Autoradiography analysis further confirmed these results; the lesion-to-remote uptake ratio with [18F]SFB-FOLand [18F]FOL were 5.7±1.8 and 3.8±0.5, respectively (P=0.14, n=3).

Conclusion: [18F]SFB-FOL was shown to be a stable radiotracerfor targeting active inflammation via FR-β in the experimentalmyocarditis model, comparable to the established [18F]FOL tracer.