Abstract 333: Thrombus-specific Manganese Nanocolloids for MR Molecular Imaging of Ruptured Plaque
Introduction: Detection of thrombus within fissures of vulnerable atherosclerotic plaques requires a sensitive molecular imaging contrast agent. The recent discovery of nephrogenic systemic fibrosis (NSF) has raised concern over the use of currently approved gadolinium based contrast agents and created a high, translational barrier for new agents to address
Objective: The goal of this research was to develop an MR T1w manganese-based molecular imaging agents with high avidity for fibrin.
Methods and Results: Manganese oxide nanocolloids (ManOC) and manganese oleate nanocolloids (ManOL) were designed and synthesized as vascularly-constrained (130 nm) nanoparticles, encapsulated by phospholipids, and characterized for MR with a Look-Locker sequence. The particulate relaxivities of the ManOC and ManOL were high, r1(ManOC)=91,127±2323 and r1(ManOL)= 423,420±10564 (s•mmol [nanoparticle])−1 measured at 3.0T (25°C) and associated with ionic r1 relaxivities of 4.1±0.9 (ManOC) and 14.6±1.1 (ManOL) (s•mmol [Mn])−1, respectively. MR imaging of manganese nanocolloids targeted to fibrin clot phantoms showed clear contrast enhancement, while control clots (non-targeted and targeted no metal) had no (p<0.05) contrast change (Fig 1⇓). In particular, the manganese oleate compound was highly stable and thermally decomposed at 325°C, likely precluding adverse ionotropic and contractility effects associated with free Mn2+.
Conclusions: Fibrin-specific manganese nanocolloids offer strong, bright (T1w) MR detection of ruptured atherosclerotic plaque without the risk of NSF.
This research has received full or partial funding support from the American Heart Association, National Center.