Evaluation of annexin V as a platelet-directed thrombus targeting agent.
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 (t1/2 = 6.4 min, 76% of radioactivity) and a slower late phase (t1/2 = 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.
Tait
J F
JF
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle 98195.
Cerqueira
M D
MD
Dewhurst
T A
TA
Fujikawa
K
K
Ritchie
J L
JL
Stratton
J R
JR
D000818:Animals; D017304:Annexin A5 / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D002341:Carotid Artery Thrombosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D007083:Iliac Artery / Q000196:embryology / Q000473:pathology / Q000502:physiology; D007457:Iodine Radioisotopes; D007668:Kidney / Q000196:embryology / Q000473:pathology / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D011817:Rabbits; D013154:Spleen / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D013552:Swine; D013927:Thrombosis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology
D017304:Annexin A5; D007457:Iodine Radioisotopes