Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe.

BACKGROUND

Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions.

MATERIALS AND METHODS

Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 (Zr). The targeting potential of this probe was compared with unspecific Zr-HSA and F-FDG in an experimental model of atherosclerosis ( mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls.

RESULTS

PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of Zr-Mal-HSA in the atherosclerotic lesions of mice. The maximum standardized uptake values (SUV) for Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (<0.05) in mice than in control WT mice, whereas no difference in SUV was observed for F-FDG in the same animals. Zr-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (<0.01) for mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (<0.001) for Zr-Mal-HSA compared with unspecific Zr-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of Zr-Mal-HSA in the aortas of mice than in WT mice (9.4±1.4 vs 0.8±0.3%; <0.001).

CONCLUSION

Zr radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of mice, as demonstrated by quantitative in vivo PET/MRI. Zr-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.