Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets
The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.
- Research Organization:
- New England Medical Center, Boston, MA (USA)
- OSTI ID:
- 6408161
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 86:3
- Country of Publication:
- United States
- Language:
- English
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MONOCLONAL ANTIBODIES
SPECIFICITY
THROMBOSIS
DIAGNOSIS
BABOONS
BIOLOGICAL MODELS
BLOOD FLOW
BLOOD PLATELETS
IODINE 123
MEMBRANE PROTEINS
RADIOIMMUNOSCINTIGRAPHY
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARDIOVASCULAR DISEASES
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
MATERIALS
MONKEYS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPE SCANNING
RADIOISOTOPES
SCINTISCANNING
VASCULAR DISEASES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics