Toward Metal-Free Magnetic Micro-Graphite as Contrast Agents for Magnetic Resonance Imaging: Synthesis, Characterization and In vitro Studies
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Approximately sixty million MRI procedures are performed annually worldwide, with 30% of these procedures using MRI contrast agents (CAs). Most commonly used clinical CAs and experimental CAs for advance molecular/cellular MRI are either paramagnetic Gd-based T1 CAs or superparamagnetic Fe-based T2 CAs. They use chelating ligands or biocompatible coatings to sequester the toxicity of naked gadolinium (Gd) and iron (Fe). But, these toxicity-sequestering strategies may not be adequate as recent reports associate clinical Gd-based agents CAs with acute renal failure. Graphitic carbon in general, is safer than naked Gd or Fe, and thus, the possibility of creating metal-free magnetic carbon CAs in a systematic and controllable way will be an exciting and tantalizing prospect. Magnetism in graphitic structures has been recently reported at room temperatures. Experimental methods adopted to induce magnetism in graphite, including the introduction of defects by irradiation of ions or electrons yield microscopic quantities of magnetic graphite. Due to poor scalability and low yields of the synthesis techniques, accurate characterization of magnetic graphite samples is challenging. Further, the presence of metallic impurities questions the very origin of magnetism in graphite, a concern yet to be comprehensively addressed. Here, a novel synthesis technique for the production of macroscopic quantities of magnetic graphite with ease of scalability is presented. This chemical synthesis technique involves fluorination of graphite samples, subjected to pyrolysis to introduce defects and followed by hydrogenation of these defect sites. Analytical grade micro-graphite particles were used for these studies. The micro-graphite samples were superparamagnetic at room temperature with magnetization values around 3-6 orders higher than other published data. Saturation magnetization for micro-graphite of about 1.5emu/g, comparable to theoretical predicted value is observed. Absence of magnetism in micro-graphite samples at all processing steps prior to hydrogenation indicates that any trace metallic impurities do not induce magnetism. Structural characterization of magnetic micro-graphite samples using spectroscopic techniques revealed an increase in the number of defects and introduction of hydrogen bonds. Relaxometry and phantom imaging studies performed on magnetic micro-graphite samples to evaluate their contrast enhancing abilities showed better reduction in spin-spin (T2) relaxation times compared to spin-lattice (T1) relaxation times. Concurrently, MRI phantom imaging studies performed to visually evaluate their efficiency as contrast agents indicated enhancement in contrast comparable to clinically used Magnevist by shortening of T2 relaxation times. Preliminary in vitro cytotoxicity studies indicate that micro-graphite showed significantly higher cell viability at the highest treatment concentration (80ng/ml) at the end of 24 hours compared to metals commonly used in contrast agents. The higher magnetization values, better yields and, the promising in vitro MRI and cytotoxicity studies on the magnetic micro-graphite open venues for their possible application as CAs for MRI.