Abstract 10971: Radiographic Imaging of Specific Glycoprotein IIb/IIIa Receptor Binding Sites Allows the Detection of Activated Platelets in Arterial Thrombosis in Mice
Introduction: Late events in atherosclerosis activate platelets Resultsing in myocardial infarction or stroke. Conformational changes of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor upon activation constitute an attractive target to depict activated platelets by molecular imaging. However, the detection of functional targets on vessel walls remains challenging. By conjugating 111Indium (In) to an antibody that selectively adheres to ligand-induced binding sites (LIBS) of activated GPIIb/IIIa, we assessed a highly sensitive radiographic Methods to specifically image activated platelets.
Methods and Results: LIBS-antibody as well as non-specific control-antibody were conjugated to 111Indium (= In-LIBS/In-control). Labelled antibodies were incubated with activated human platelets in vitro. Autoradiographic analysis demonstrated a significantly increased signal emission intensity after incubation with In-LIBS compared to In-control indicating a specific binding of In-LIBS to activated platelets (In-LIBS: 4132±198.5 digital light units (DLU)/mm2 vs. In-control: 2049±94.38 DLU/mm2; p< 0.001). We then applied these findings to an ex-vivo mouse model. After induction of a wall adherent non-occlusive thrombosis in carotid arteries, we injected In-LIBS or In-control intravenously. After 30min of circulation time, animals were sacrificed, carotid arteries resected and exposed to an autoradiographic phosphor imaging system. Again, we could demonstrate a remarkable increased signal emission after injection of In-LIBS compared to In-control. Presence of thrombi in carotid arteries was confirmed by histology.
Conclusions: Targeting the functional LIBS-epitope of glycoprotein IIb/IIIa receptor on platelets allows specific imaging of activated platelets. Mouse data also illustrate the potential of this approach to image wall-adherent arterial thrombosis with high sensitivity. These data encourage further studies on an early detection of arterial thrombosis using this technique, which would be of clinical relevance for the timely initiation of medical/interventional therapy in atherothrombotic disease.
- © 2010 by American Heart Association, Inc.