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

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

Ahmed, M. (author)

Tegnebratt, T. (author)

Tran, T. A. (author)

Damberg, P. (author)

Gistera, A. (author)

Tarnawski, L. (author)

Bone, D. (author)

Hedin, U. (author)

Eriksson, P. (author)

Holmin, S. (author)

Gustafsson, B. (author)

Caidahl, Kenneth, 1949 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine

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2020
2020
English.
In: International Journal of Nanomedicine. - 1178-2013. ; 15, s. 6137-6152

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.2...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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-89(4+)). The targeting potential of this probe was compared with unspecific Zr-89-HSA and F-18-FDG in an experimental model of atherosclerosis (Apoe(-/-) 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-89-Mal-HSA in the atherosclerotic lesions of Apoe(-/-) mice. The maximum standardized uptake values (SUVmax) for Zr-89-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe(-/-) mice than in control WT mice, whereas no difference in SUVmax was observed for F-18-FDG in the same animals. Zr-89-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (P<0.01) for Apoe(-/-) mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (P<0.001) for Zr-89-Mal-HSA compared with unspecific Zr-89-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-89-Mal-HSA in the aortas of Apoe(-/-) mice than in WT mice (9.4 +/- 1.4 vs 0.8 +/- 0.3%; P<0.001). Conclusion: Zr-89 radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of Apoe(-/-) mice, as demonstrated by quantitative in vivo PET/MRI. Zr-89-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)

Keyword

positron emission tomography
molecular imaging
zirconium
human serum
albumin
atherosclerosis
macrophages
macrophage scavenger receptor
plaque inflammation
class-a
expression
accumulation
atorvastatin
adhesion
cells
Science & Technology - Other Topics
Pharmacology & Pharmacy

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ref (subject category)
art (subject category)

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By the author/editor: Ahmed, M.; Tegnebratt, T.; Tran, T. A.; Damberg, P.; Gistera, A.; Tarnawski, L.; show more...; Bone, D.; Hedin, U.; Eriksson, P.; Holmin, S.; Gustafsson, B.; Caidahl, Kenneth ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

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By the university: University of Gothenburg

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