18F-FOL PET imaging demonstrated increased uptake in the aortic valve of CAVD mice, indicating heightened inflammation as evidenced by macrophage infiltration (TBRmean 1.9 vs. 1.1, p<0.0001).
Does 18F-FOL PET imaging detect aortic valve inflammation in a mouse model of calcific aortic valve disease compared to healthy controls?
18F-FOL PET imaging successfully detects macrophage-associated active inflammation in the aortic valves of a mouse model of calcific aortic valve disease.
Absolute Event Rate: 0% vs 0%
Abstract Background Inflammation, characterized by infiltration of macrophages, contributes to fibro-calcific leaflet remodeling in calcific aortic valve disease (CAVD). Folate receptor β (FR-β) is a membrane-bound protein upregulated on activated macrophages and therefore represents a potential target for in vivo imaging of inflammation (1, 2). Purpose We evaluated Al18F-NOTA-folate (18F-FOL), a positron emission tomography (PET) tracer targeting FR-β, for its ability to assess aortic valve inflammation in a mouse model of CAVD. Methods One-year-old atherosclerotic LDLR-/-ApoB100/100 mice (n=8) fed with a high-fat diet for 7-8 months were used as an experimental model of CAVD. Healthy, age matched C57BL/6N mice (n=8) fed with a regular chow diet served as controls. Echocardiography was performed to detect aortic stenosis. The mice underwent 18F-FOL PET, 18F-NaF PET (microcalcification), and contrast-enhanced computed tomography (CT) imaging. Target-to-background (TBR) ratios (valve-to-blood) were calculated from mean standardized uptake values (SUV) at 50-60 min after tracer injection. The uptake of 18F-FOL in the aortic valve was studied in more detail by ex vivo autoradiography of tissue sections, coupled with histological analyses. Results Doppler echocardiography demonstrated elevated transvalvular peak flow velocity in CAVD mice compared to healthy controls, indicating the presence of aortic stenosis (1400±250 vs. 650±210 mm/s, p0.001). Moreover, left ventricular ejection fraction was reduced in CAVD mice compared to controls (53±4.8 vs. 60±2.3 %, p=0.004). PET/CT imaging revealed increased 18F-FOL and 18F-NaF uptake in the aortic valve region of CAVD mice, coinciding with thickened leaflets and mild calcification in histology. Quantitatively, the uptake of both tracers was significantly higher in the diseased valve compared to healthy valve of control mice (TBRmean: 18F-FOL 1.9±0.34 vs. 1.1±0.08, p0.0001, and 18F-NaF 1.8±0.47 vs. 1.1±0.22, p=0.001). Autoradiography confirmed focal accumulation of 18F-FOL in valve leaflets of CAVD mice (valve-to-myocardium ratio: 2.4±0.47 vs. 1.7±0.27, p=0.008). Furthermore, immunohistochemical staining of corresponding valve sections showed macrophage (Mac-3)-positive areas in CAVD mice compared to controls (0.056±0.017 vs. 0.035±0.011 mm2, p=0.018). (Figure 1) Conclusion Uptake of 18F-FOL is increased in valve leaflets exhibiting macrophage infiltration in a mouse model of CAVD. These results suggest that 18F-FOL is a potential PET tracer for the assessment of active inflammation associated with CAVD.Figure 1
Stahle et al. (Thu,) reported a other. 18F-FOL PET imaging demonstrated increased uptake in the aortic valve of CAVD mice, indicating heightened inflammation as evidenced by macrophage infiltration (TBRmean 1.9 vs. 1.1, p<0.0001).