Abstract 1659: MRI Efficacy of Spherical and Discoidal Gadolinium-Labeled ApoA-I/phospholipid Nanoparticles in the Vessel Wall of ApoE-/- Mice
Introduction: High-density lipoproteins (HDL) naturally target atherosclerotic plaque. Previously, spherical gadolinium labeled HDL (Gd-sHDL) nanoparticles have been used to target plaque in ApoE-/- mice. It has been hypothesized that discoidal HDL (Gd-dHDL) may be more effective due to their reduced transverse dimension.
Aim: To synthesize, characterize, and compare the in vivo efficacy of spherical and discoidal HDL in ApoE-/- mice.
Methods: Gd-sHDL was prepared using human apoA-I, a surface lipid (POPC), GdDTPA-bis(steryl-amide), a fluorescent label, and a cholesteryl ester for the core. Gd-dHDL was prepared similarly, but omitting the core lipid. The size and in vitro MR efficacy was determined. One year old ApoE-/-and wild type (WT) mice were administered 5 umol Gd/Kg of Gd-sHDL or Gd-dHDL. Images of the abdominal aorta were obtained at 9.4T over a six-day period post injection (pi). The signal enhancement (%NENH), relative to muscle, was determined.
Results: Gd-dHDL showed consistently higher wall enhancement, relative to Gd-sHDL (Table 1⇓, Fig. 1⇓) For Gd-dHDL re-circulation into the wall was observed 6 days pi. No significant enhancement was observed in WT mice.
Conclusions: Gd-dHDL may be more effective than Gd-sHDL for enhancing the MR signal of plaque. The results suggest it may be possible to visualize the re-circulation of Gd-dHDL in the vessel wall of ApoE-/- mice.