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

T Dietrich, D Berndorff, T Heinrich, T Hucko, E Stepina, P Hauff, L M Dinkelborg, K Atrott, L Giovannoni, D Neri, E Fleck, K Graf, H D Menssen
Quarterly Journal of Nuclear Medicine and Molecular Imaging 2015, 59 (2): 228-37

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 [(99m)Tc]-conjugated AP39 ([(99m)Tc]-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 [(99m)Tc]-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 [(99m)Tc]-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: [(99m)Tc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.

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