ORIGINAL ARTICLES   

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

Copyright © 2015 EDIZIONI MINERVA MEDICA

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.