Detection of thrombus within fissures of vulnerable atherosclerotic plaques requires a sensitive yet safer contrast agent for magnetic resonance imaging. The recent discovery of nephrogenic systemic fibrosis (NSF) has raised concern over the use of currently approved gadolinium based contrast agents in patients with renal/kidney diseases and created a high, translational barrier for new agents to address.  With this aim in our mind, we explore for the first time dual paramagnetic metal manganese (Mn) and copper (Cu) for a consolidated and synchronous effect from these metals.  The goal of this study was to develop a sensitive 'hybrid' Mn-Cu-based molecular imaging agents with high avidity for fibrin.  �Soft� type nano colloids were designed and synthesized as vascularly-constrained (Dav=200 nm, z=-23mV) nanoparticles with a core entrapped manganese oleate and a shell presenting copper (II)-DTPA. Organically soluble Mn (II) oleate was suspended in polysorbate and encapsulated by phospholipid mixture to incorporate nominally 100,000 Mn/particle and 20,000 Cu(II)-DTPA per particle. For in vitro targeting, ligand biotin was used as a component of the lipid surfactant. A single slice inversion recovery sequence was used to calculate the particulate (per particle) relaxivities of serially diluted nanoparticles. Fibrin clots supported on silk suture suspended in PBS were targeted with biotinylated NanoCool or control nanocolloids to the fibrin clots with avidin-biotin interactions and fibrin-specific antibodies (NIB5F3). MR images (3T) of the clots were acquired using T1-weighted gradient echo images. MR imaging of targeted and non-targeted particles to fibrin clot phantoms showed clear contrast enhancement, while control clots (non-targeted and targeted without metals) had no (or negligible, p<0.05) contrast changes.  Fibrin-specifichybrid Mn-Cu nanoparticles offer high relaxivity, non-gadolinium imaging agents for sensitive noninvasive MRI of human thrombus.

Synergistic effect of two paramagnetic metals in a single nanocolloid for enhanced magnetic resonance imaging

248th National Meeting (2014)

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