title: The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques.
abstract: We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR. Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDL's effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues.
authors.affiliation: Leon H. Charney Division of Cardiology and Marc and Ruti Bell Program in Vascular Biology, Department of Medicine, New York University School of Medicine, Smilow 7, 522 First Avenue, New York, New York 10016, United States.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barazza
authors.forename: Courtney
authors.initials: C
authors.lastname: Blachford
authors.forename: Orli
authors.initials: O
authors.lastname: Even-Or
authors.forename: Victor A
authors.initials: VA
authors.lastname: Joaquin
authors.forename: Karen C
authors.initials: KC
authors.lastname: Briley-Saebo
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: David P
authors.initials: DP
authors.lastname: Cormode
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D005682:Gadolinium / Q000097:blood / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry; D018810:Magnetic Resonance Angiography; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000175:diagnosis*; D011973:Receptors, LDL / Q000172:deficiency
chemical_list: D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D009942:Organometallic Compounds; D011973:Receptors, LDL; D005682:Gadolinium