Uptake of 68gallium in atherosclerotic plaques in LDLR-/-ApoB100/100 mice View Full Text


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Article Info

DATE

2011-12

AUTHORS

Johanna MU Silvola, Iina Laitinen, Henri J Sipilä, V Jukka O Laine, Pia Leppänen, Seppo Ylä-Herttuala, Juhani Knuuti, Anne Roivainen

ABSTRACT

BACKGROUND: Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice. METHODS: Uptake of ionic 68Ga was investigated in atherosclerotic LDLR-/-ApoB100/100 and C57BL/6N control mice at 3 h after injection. The ex vivo biodistribution of the 68Ga was assessed and autoradiography of aortic cryosections was defined. In vivo imaging of 68Ga was performed using a small animal positron emission tomography PET/CT scanner. RESULTS: Our results revealed that the uptake of 68Ga-radioactivity was higher in atherosclerotic plaques than in healthy vessel wall (ratio 1.8 ± 0.2, p = 0.0002) and adventitia (ratio 1.3 ± 0.2, p = 0.0011). The autoradiography signal co-localized with macrophages prominently as demonstrated by Mac-3 staining. In both mice strains, the highest level of radioactivity was found in the blood. CONCLUSIONS: We observed a moderate but significantly elevated 68Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. While the uptake of 68Ga was promising in this animal model, the slow blood clearance may limit the usability of 68Ga as a PET tracer for clinical imaging of atherosclerotic plaques. More... »

PAGES

14

References to SciGraph publications

  • 2005-11. Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2007-12. What can gallium-68 PET add to receptor and molecular imaging? in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2009-12. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 1987-02. 67Ga accumulation in inflammatory lesion and its mechanism: Comparison with malignant tumor in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2004-01. Positron flight in human tissues and its influence on PET image spatial resolution in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2005-06. Mechanisms of Disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosis in NATURE REVIEWS CARDIOLOGY
  • 1996-04. The uptake mechanisms of inflammation-and infection-localizing agents in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2006-12. Non-specific binding of [18F]FDG to calcifications in atherosclerotic plaques: experimental study of mouse and human arteries in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2010-06. 68Ga-Chloride PET Reveals Human Pancreatic Adenocarcinoma Xenografts in Rats—Comparison with FDG in MOLECULAR IMAGING AND BIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/2191-219x-1-14

    DOI

    http://dx.doi.org/10.1186/2191-219x-1-14

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22214258


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    27 schema:description BACKGROUND: Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice. METHODS: Uptake of ionic 68Ga was investigated in atherosclerotic LDLR-/-ApoB100/100 and C57BL/6N control mice at 3 h after injection. The ex vivo biodistribution of the 68Ga was assessed and autoradiography of aortic cryosections was defined. In vivo imaging of 68Ga was performed using a small animal positron emission tomography PET/CT scanner. RESULTS: Our results revealed that the uptake of 68Ga-radioactivity was higher in atherosclerotic plaques than in healthy vessel wall (ratio 1.8 ± 0.2, p = 0.0002) and adventitia (ratio 1.3 ± 0.2, p = 0.0011). The autoradiography signal co-localized with macrophages prominently as demonstrated by Mac-3 staining. In both mice strains, the highest level of radioactivity was found in the blood. CONCLUSIONS: We observed a moderate but significantly elevated 68Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. While the uptake of 68Ga was promising in this animal model, the slow blood clearance may limit the usability of 68Ga as a PET tracer for clinical imaging of atherosclerotic plaques.
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