title: Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis.
abstract: 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 7.5 mol% 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%, ∼0.22 mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2 = 422 s(-1) mM(-1) and r2(∗) = 452 s(-1) mM(-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 ex vivo. 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.
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Meier
authors.affiliation: Department of Clinical Chemistry, University Hospital Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Pütz
authors.affiliation: Department of Clinical Research, Tumor Biology Center Freiburg, Germany; Andreas Hettich GmbH & Co KG, Tuttlingen, Gemany.
authors.forename: U
authors.initials: U
authors.lastname: Massing
authors.affiliation: Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia.
authors.forename: C E
authors.initials: CE
authors.lastname: Hagemeyer
authors.affiliation: Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: von Elverfeldt
authors.affiliation: Department of Diagnostic Radiology Medical Physics, University Hospital Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Meissner
authors.affiliation: Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia; Atherothrombosis and Vascular Laboratory, Baker IDI, Melbourne, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Ardipradja
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Barnert
authors.affiliation: Atherothrombosis and Vascular Laboratory, Baker IDI, Melbourne, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Peter
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bode
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Germany. Electronic address: constantin.vonzurmuehlen@universitaets-herzzentrum.de.
authors.forename: C
authors.initials: C
authors.lastname: von zur Muhlen
mesh_terms: D001792:Blood Platelets / Q000737:chemistry*; D003287:Contrast Media; D006801:Humans; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D013927:Thrombosis / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D008081:Liposomes
keywords: Atherosclerosis; Liposomes; MRI; Magnetoliposomes; Platelets; SPIO