255 In vivo detection of non-occlusive thrombi in drug-eluting stents by scintigraphy and radio-labelled annexin V in a rabbit model

Abstract

Thrombi in contact with non re-endothelialized stent struts associated with drug-eluting stent (DES) thrombosis. Hence, detection of thrombi in DES could help to evaluate the risk of DES thrombosis. Annexin V radio-labelled with 99 mTechnetium (99 mTc) is a radio-tracer with a high affinity for activated platelets. Our objectives were: 1) to develop an animal model of non-occlusive thrombosis of stents, 2) to evaluate the ability of annexin V 99 mTc for the detection of in-stent thrombi using scintigraphy. Right carotid arteries of NZW rabbits (n = 14) fed a high cholesterol diet were implanted with overlapping DES (n = 7) or bare-metal stents (BMS; n = 7). Four weeks after stent implantation, rabbits underwent a first scintigraphy 3 hours after injection of 200 MBq of radio-labelled annexin V 99 mTc. At the end of the first scintigraphy, a suture was placed surgically proximal to the stented carotid arteries in order to induce a thrombus-prone flow limiting stenosis. Four days later, a second scintigraphy was performed. After the second scintigraphy, stents were excised, imaged ex vivo and then fixed for histological examination and scanning electron microscopy (SEM). Activities measured in vivo in the stented carotid arteries after injection of annexin V 99 mTc were higher on the second scintigraphy after creation of a surgical stenosis as compared to the first scintigraphy (0.24 vs. 0.15 counts/pixel/MBq, respectively; p<0.05). On the second scintigraphy, activities were higher in DES vs. BMS (0.26 vs. 0.19 counts/pixel/MBq, respectively; p < 0.005). High activities measured in stents in vivo were associated with the detection of thrombi on corresponding histological sections and SEM. In this work, we developed a rabbit model of non-occlusive thrombosis of stents in carotid arteries. In this model, in-stent thrombi could be detected using annexin V 99 mTc scintigraphy.