Physicochemical characterization of a novel graphene-based magnetic resonance imaging contrast agent

Abstract

Shruti Kanakia,1 Jimmy D Toussaint,1 Sayan Mullick Chowdhury,1 Gaurav Lalwanim,1 Tanuf Tembulkar,1 Terry Button,1,2 Kenneth R Shroyer,3 William Moore,2 Balaji Sitharaman11Department of Biomedical Engineering, 2Department of Radiology, 3Department of Pathology, Stony Brook University, Stony Brook, NY, USAAbstract: We report the synthesis and characterization of a novel carbon nanostructure-based magnetic resonance imaging contrast agent (MRI CA); graphene nanoplatelets intercalated with manganese (Mn2+) ions, functionalized with dextran (GNP-Dex); and the in vitro assessment of its essential preclinical physicochemical properties: osmolality, viscosity, partition coefficient, protein binding, thermostability, histamine release, and relaxivity. The results indicate that, at concentrations between 0.1 and 100.0 mg/mL, the GNP-Dex formulations are hydrophilic, highly soluble, and stable in deionized water, as well as iso-osmolar (upon addition of mannitol) and iso-viscous to blood. At potential steady-state equilibrium concentrations in blood (0.1–10.0 mg/mL), the thermostability, protein-binding, and histamine-release studies indicate that the GNP-Dex formulations are thermally stable (with no Mn2+ ion dissociation), do not allow non-specific protein adsorption, and elicit negligible allergic response. The r1 relaxivity of GNP-Dex was 92 mM-1s-1 (per-Mn2+ ion, 22 MHz proton Larmor frequency); ~20- to 30-fold greater than that of clinical gadolinium (Gd3+)- and Mn2+-based MRI CAs. The results open avenues for preclinical in vivo safety and efficacy studies with GNP-Dex toward its development as a clinical MRI CA.Keywords: manganese, dextran, preclinical, physicochemical properties, relaxivity, graphene, magnetic resonance imaging, contrast agent