Physicochemical characterization of a novel graphene-based magnetic resonance imaging contrast agent.
We report the synthesis and characterization of a novel carbon nanostructure-based magnetic resonance imaging contrast agent (MRI CA); graphene nanoplatelets intercalated with manganese (Mn(2+)) 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 Mn(2+) ion dissociation), do not allow non-specific protein adsorption, and elicit negligible allergic response. The r 1 relaxivity of GNP-Dex was 92 mM(-1)s(-1) (per-Mn(2+) ion, 22 MHz proton Larmor frequency); ~20- to 30-fold greater than that of clinical gadolinium (Gd(3+))- and Mn(2+)-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.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281 , USA.
Shruti
S
Kanakia
Jimmy D
JD
Toussaint
Sayan Mullick
SM
Chowdhury
Gaurav
G
Lalwani
Tanuf
T
Tembulkar
Terry
T
Button
Kenneth R
KR
Shroyer
William
W
Moore
Balaji
B
Sitharaman
D055598:Chemical Phenomena; D003287:Contrast Media / Q000737:chemistry*; D003911:Dextrans; D005682:Gadolinium; D006108:Graphite / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D049329:Nanostructures / Q000737:chemistry*; D019047:Phantoms, Imaging; D013818:Thermogravimetry
D003287:Contrast Media; D003911:Dextrans; D008345:Manganese; D006108:Graphite; D005682:Gadolinium
contrast agent; dextran; graphene; magnetic resonance imaging; manganese; physicochemical properties; preclinical; relaxivity