Abstract 14636: Hybrid Manganese Nanocolloid with Ultralow Gadolinium Affords T1w MR Molecular Imaging of Atherosclerotic Angiogenesis

Abstract

Background: MR molecular imaging of plaque angiogenesis using targeted nanoparticles with high payloads of gadolinium (Gd) has clinical importance as a biosignature, but the issue of NSF has compelled efforts to reduce Gd exposure.

Objective: 1) to design and characterize an ultralow Gd-manganese-oleate nanocolloid (Gd-MnOL-NC); 2) to demonstrate efficacy of αvβ3-Gd-MnOL-NC in hyperlipidemic rabbits; and 3) to develop 3D mapping and indexing strategies for characterizing atherosclerotic angiogenesis.

Methods and Results: Hybrid lipid-encapsulated nanocolloids were synthesized with a manganese-oleate in polysorbate core and titrated surface levels of two lipid-anchored gadolinium chelates (Gd-ManOL-NP). Nanocolloids incorporating 1.25 mol% Gd-DOTA-phosphoethanolamine into the surfactant (size: 138±10nm; PDI: 0.06; zeta: -27±2 mV) produced an unexpected synergistic magnetic interaction with the Mn-rich core and increased T1 particulate relaxivity (3T, 25C) (748,199±30,464 (s·mmol [Gd-ManOL-NC]) -1) versus MnOL-NC alone (590,301±27,556 (s·mmol [ManOL NC]) -1) or 1.25 mol% Gd-oil-NC (19,933±165 (s·mmol [Gd-oil-NC])-1) NPs. While ανβ3-MnOL-NCs were ineffective for angiogenesis imaging in rabbits, ανβ3-Gd-MnOL-NC provided high neovascular contrast at 2 hrs. The percent area of angiogenesis in hyperlipidemic rabbits receiving αvβ3-Gd-MnOL-NC was higher (24.4±3.0 %, p < 0.05) than that measured with non-targeted MnOL-Gd (14.6±3.3 %) or in controls given ανβ3-Gd-MnOL-NC (12.6±3.0%). Complement activation in pooled human serum and in mice was neglible. 3D maps provided high-resolution visualization of vasa vasorum neovascular expansion, which was not observed in animals given nontargeted-MnOL-Gd (Fig) Conclusions Unexpected synergism between ultralow surface Gd-DOTA-lipid and the manganese-oleate core afforded highly sensitive 3D imaging of angiogenesis in vivo.