Abstract 1915: ApoE derived lipopeptide containing Gadolinium mixed Micelles for Macrophage Imaging in ApoE ko Mice
Introduction: Apolipoprotein E derived Lipopeptide-P2A2 consists of a 10 amino acid tandem dimer covalently bound to two acyl chains. The peptide sequence of P2A2 comprises binding sites for the low-density lipoprotein receptor and cell surface heparan sulfate proteoglycans. P2A2 containing lipid particles have been shown to be taken up by endothelial cells in vitro. Our group has previously shown that non-targeted Gadolinium mixed micelles can localize to areas rich in extracellular matrix in atherosclerotic plaque without cellular interaction. This study was designed to demonstrate the enhanced cellular binding properties of Gadolinium mixed micelles after P2A2 incorporation.
Methods: Atherosclerotic ApoE −/− and normal (wt) mice underwent in vivo MRI of the abdominal aorta using a 9.4T MR system 24h after injection of P2A2 containing Gadolinium mixed micelles (“ApoE-Micelles”). As a control, ApoE−/− mice were injected with untargeted micelles. Another control group was injected with Gd-DTPA. Frozen sections were obtained and imaged using confocal microscopy. In vitro studies with incubation of ApoE -and untargeted micelles in RAW 264.7 cells were performed.
Results: The administration of untargeted and ApoE micelles resulted in a significant enhancement (relative to muscle) of the vessel wall of ApoE−/− mice. %NENH: 57% +/−1.5, and 102.1% +/−8.8 respectively. Following administration of Gd-DTPA no significant enhancement of the vessel wall was observed. Confocal microscopy demonstrated the specific co-localization of ApoE micelles to macrophages. In contrast, untargeted micelles showed no cellular interaction. In vitro studies in RAW 264.7 cells confirmed the specific uptake of ApoE micelles in macrophages. No uptake was detected in these cells using untargeted micelles.
Conclusion: P2A2 containing gadolinium mixed micelles are a promising new agent for macrophage imaging in atherosclerotic plaque by MRI.