Abstract 10321: Molecular MRI of Activated Platelets Using Anti-LIBS-magnetoliposomes as a New Strategy for Timely Detection of Unstable Plaques
Introduction: Early and noninvasive detection of unstable atherosclerotic plaques would be of great clinical importance. Activated platelets are an interesting molecular target for detection of early lesions or unstable plaques. Therefore, we are developing a MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand induced binding site of the activated gpIIb/IIIa receptor of platelets.
Methods: The specific binding of fluorescently labeled anti-LIBS-MLs to the activated gpIIb/IIIa receptor in vitro was determined with a flow cytometer experiment of human platelets as well as with an immunostaining experiment of CHO cells expressing the activated gpIIb/IIIa receptor. As control groups, MLs linked to an unspecific antibody or MLs without antibody were used. An in vivo MRI-study was performed in order to image the specific targeting of activated platelets with LIBS-MLs in a murine model of ferric chloride-induced arterial thrombosis. Afterwards, the carotid artery was removed and analyzed by histology.
Results: Specific targeting of the activated gpIIb/IIIa receptor in vitro could be achieved with the anti-LIBS-MLs. The median fluorescence intensity of human platelets incubated with the anti-LIBS-MLs measured by flow cytometry significantly increased compared to the control groups, and this specific targeting was also seen in the immunostaining experiment. The preliminary data of the in vivo MRI-study showed a binding of anti-LIBS-MLs to the injured area of the carotid artery. This could also be confirmed by histology and fluorescence microscopy.
Conclusion: In this study, we demonstrate that activated platelets can be targeted in vitro and in vivo by anti-LIBS MLs. These data obtained from immunomagnetoliposomes are an important step towards developing a human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.
- © 2013 by American Heart Association, Inc.