Abstract 17074: T1-Weighted MR Imaging of Aortic Angiogenesis in Rabbits with an Ultralow New Low Gadolinium

Abstract

Background: The recent discontinuation of the AIM-HIGH study suggests that even HDL and TG levels do not adequately predict cardiovascular disease outcome. Angiogenesis, an integrated intramural biomarker of plaque progression, has been quantitatively and rapidly used for T1-weighted MR imaging with targeted gadolinium nanoparticles (PFC NPs), but new agents with even lower lanthanide levels are desired. Objective: We hypothesized that targeted manganese-oleate core NCs that present 30-fold less Gd than PFC NPs could provide strong, T1-weighted MR imaging of neovascular α v β 3 -integrin expression in vivo. Methods and Results: Vascularly-constrained (D av =140 nm, ζ=-13mV) nanocolloids (NC) of Mn oleate (20% v/v) were synthesized using only 1.25mole% of Gd as (versus 30 mole% for PFC NPs), 0.25 mole% of a quinolone-derived α v β 3 -integrin antagonist, and 98.5 mole% lecithin. Cholesterol fed New Zealand White rabbits (n=8/group) received α v β 3 -Mn(Gd)-NC or nontargeted Mn(Gd)-NC i.v. (1ml/kg); 8 rabbits on normal chow received α v β 3 -Mn(Gd)-NC. Dynamic MR imaging (3.0T) of the descending thoracic aorta wall revealed a marked signal enhancement (47±5%) at 2h. In comparison, the nontargeted-MnGd-NC had lower (20±5%) signal enhancement than targeted NPs (p<0.05). Rabbits fed a normal diet and treated with α v β 3 -MnGd NP had the lowest signal increase, 12±3%, which did not differ from the nontargeted treatment. Histology corroborated the prominent, neointimal proliferation among cholesterol-fed, and homing specificity. Conclusions: Angiogenesis imaging offers a direct intramural measure of atherosclerotic disease progression and α v β 3 -Mn(Gd)-NC provides a sensitive MR molecular imaging approach with gadolinium decreased to 300-fold less than clinical single dose Gd-DTPA.