Polyurethane based organic macromolecular contrast agents (PU-ORCAs) for magnetic resonance imaging

Abstract

Magnetic resonance imaging (MRI) is one of the leading imaging modalities because of the combination of convenient non-invasive application, high spatial resolution, and tomographic capability. MRI is not as sensitive as other techniques, and gadolinium (Gd(III)) based contrast agents must be added to increase the spatial resolution. Recent studies demonstrated that Gd(III) based contrast agents are not completely released from the body after treatment, which can cause damage, especially in renal impaired patients such as the nephrogenic systemic fibrosis (NSF) due to the toxicity of free Gd(III). In this context, we synthesize gadolinium-free macromolecular contrast agents, PU-ORCAs (polyurethane based organic contrast agents) containing nitroxides for MRI. Nitroxides are stable, organic, free radicals with a single unpaired electron, showing a potential for MRI applications. First, we successfully synthesize an MRI active novel diol monomer containing a nitroxide. Afterwards we copolymerize the nitroxide containing diol with polyethylene glycol end-capped diol and hexamethylene diisocyanate in the presence of the diazabicyclo[5.4.0]undec-7-ene (DBU) catalyst to prepare the macromolecular polyurethane based contrast agents. The ability of these amphiphilic polyurethanes to self-assemble in water is demonstrated. In addition, we show that PU-ORCAs are able to increase the water proton relaxivity (r1) and (r2), at 1.5 T, up to 0.66 and 0.98 mM-1 s-1 respectively. Phantom studies confirm that in the presence of low PU-ORCA concentrations (3.3 mM) there is a significant contrast enhancement, especially in the T1-imaging modality. In addition, r2/r1 = 1.3 value is close to 1 in human serum.