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Rivista di Medicina Nucleare e Imaging Molecolare

A Journal on Nuclear Medicine and Molecular Imaging
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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2015 June;59(2):228-37

lingua: Inglese

Targeted ED-B fibronectin SPECT in vivo imaging in experimental atherosclerosis

Dietrich T. 1, Berndorff D. 2, Heinrich T. 2, Hucko T. 1, Stepina E. 2, Hauff P. 2, Dinkelborg L. M. 6, Atrott K. 1, Giovannoni L. 3, Neri D. 4, Fleck E. 1, Graf K. 1, 5, Menssen H. D. 3

1 Department of Medicine, Cardiology Deutsches Herzzentrum, Berlin, Germany;
2 Bayer Healthcare Pharmaceuticals, Berlin, Germany;
3 Philogen S.p.A., Siena, Italy;
4 ETH Zurich, Switzerland;
5 Department of Medicine Jüdisches Krankenhaus, Berlin, Germany;
6 Piramal Imaging GmbH, Berlin, Germany


AIM: The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [99mTc]-conjugated AP39 ([99mTc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice.
METHODS: Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [99mTc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry.
RESULTS: In vivo [99mTc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236±40.646 cpm/cm3) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468±4.976 cpm/cm3) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P<0.01).
CONCLUSION: [99mTc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.

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