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Meier S.,Albert Ludwigs University of Freiburg | Putz G.,University Hospital Freiburg | Massing U.,Tumor Biology Center Freiburg | Massing U.,Andreas Hettich GmbH and Co KG | And 10 more authors.
Biomaterials | Year: 2015

To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an 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. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5mol% positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs (~86%, ~0.22mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2=422s-1mM-1 and r2*=452s-1mM-1) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor's activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor exvivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets. © 2015 Elsevier Ltd. Source

Alt K.,Baker IDI Heart and Diabetes Institute | Alt K.,Atherothrombosis and Vascular Laboratory | Paterson B.M.,University of Melbourne | Ardipradja K.,Baker IDI Heart and Diabetes Institute | And 19 more authors.
Molecular Pharmaceutics | Year: 2014

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFvanti-LIBS) conjugated to a positron emitting copper-64 complex of a cage amine sarcophagine chelator (MeCOSar) is reported. This tracer was compared in vitro to a 64CuII complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate was radiolabeled with 64CuII rapidly under mild conditions and with higher specific activity than scFvanti-LIBS-DOTA. The utility of scFvanti-LIBS-MeCOSar as a diagnostic agent was assessed in vivo in a mouse model of acute thrombosis. The uptake of scFvanti-LIBS- 64CuMeCOSar in the injured vessel was significantly higher than the noninjured vessel. Positron emission tomography (PET) was used to show accumulation of scFvanti-LIBS-64CuMeCOSar with high and specific uptake in the injured vessel. ScFvanti-LIBS- 64CuMeCOSar is an excellent tool for highly sensitive in vivo detection of activated platelets in PET and has the potential to be used for early diagnosis of acute thrombotic events. © 2014 American Chemical Society. Source

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