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

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 Sitharaman<sup>1

1</sup>Department of Biomedical Engineering, ²Department of Radiology, ³Department of Pathology, Stony Brook University, Stony Brook, NY, USA

Abstract: 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