EVALUATION ON ANNEXIN-V AS A PLATELET-DIRECTED THROMBUS TARGETING AGENT

Annexin V is a human phospholipid binding protein (M(r) 36,000) that b inds with high affinity to activated platelets in vitro. We studied th e biodistribution and thrombus binding of annexin V in rabbit and swin e models of fully occlusive arterial thrombi formed 1-2 h prior to inj ection of annexin V. Iodinated annexin V was cleared from blood in a r apid 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 musc le. Thrombus/blood uptake ratios were (mean +/- SEM): 6.39 +/- 1.80 fo r rabbit iliac artery, 6.97 +/- 1.45 for swine carotid artery, and 7.6 8 +/- 1.70 for swine femoral artery (all p values < 0.01 versus contro l artery); a control protein, ovalbumin, showed an uptake ratio of 0.5 9 +/- 0.08 in swine femoral artery thrombi. These results indicate tha t annexin V is useful as an agent for selective targeting of platelet- containing thrombi.