Feasibility of [18F]-RGD for ex vivo imaging of atherosclerosis in detection of αvβ3 integrin expression

Reza Golestani, Leila Mirfeizi, Clark J Zeebregts, Johanna Westra, Hans J de Haas, Andor W J M Glaudemans, Michel Koole, Gert Luurtsema, René A Tio, Rudi A J O Dierckx, Hendrikus H Boersma, Philip H Elsinga, Riemer H J A Slart
Journal of Nuclear Cardiology 2015, 22 (6): 1179-86

BACKGROUND: Inflammation and angiogenesis play an important role in atherosclerotic plaque rupture. Therefore, molecular imaging of these processes could be used for determination of rupture-prone atherosclerotic plaques. αvβ3 integrin is involved in the process of angiogenesis. Targeted imaging of αvβ3 integrin has been shown to be possible in previous studies on tumor models, using radiolabeled arginine-glycine-aspartate (RGD). Our aim was to investigate feasibility of ex vivo detection of αvβ3 integrin in carotid endarterectomy (CEA) specimens.

METHODS AND RESULTS: Nineteen CEA specimens were incubated in 5 MBq [18F]-RGD-K5 for 1 hour followed by 1 hour emission microPET scan. The results were quantified in 4 mm wide segments as percent incubation dose per gram (%Inc/g). Segmental-to-total ratio was calculated and presence of αvβ3 integrin and endothelial cells in each segment was confirmed by immunohistochemical staining for CD31 and αvβ3 integrin, respectively. [18F]-RGD-K5 uptake was heterogeneously distributed across CEA specimens and was localized within the vessel wall. Significant correlations were observed between segmental-to-total ratio with αvβ3 integrin staining score (r = 0.58, P = .038) and CD31 staining score (ρ = 0.67, P < .002).

CONCLUSION: This study showed the feasibility of integrin imaging by determination of αvβ3 integrin expression in human atherosclerotic plaques.

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