Evaluation of annexin V as a platelet-directed thrombus targeting agent

Abstract

Annexin V is a human phospholipid binding protein (M r 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1–2 h prior to injection of annexin V. Iodinated annexin V was cleared from blood in a rapid early phase ( t 1 2 = 6.4 min, 76% of radioactivity) and a slower late phase ( t 1 2 = 71 min, 24% of radioactivity). Organ uptake was highest in the kidney and spleen and lowest in heart and skeletal muscle. Thrombus/blood uptake ratios were (mean ± SEM): 6.39 ± 1.80 for rabbit iliac artery, 6.97 ± 1.45 for swine carotid artery, and 7.68 ± 1.70 for swine femoral artery (all p values < 0.01 versus control artery); a control protein, ovalbumin, showed an uptake ratio of 0.59 ± 0.08 in swine femoral artery thrombi. These results indicate that annexin V is useful as an agent for selective targeting of platelet-containing thrombi.