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Safety and efficacy of a high-performance graphene-based magnetic resonance imaging contrast agent for renal abnormalities

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Abstract

The etiology of renal insufficiency includes primary (e.g., polycystic kidney disease) or secondary (e.g., contrast media, diabetes) causes. The regulatory restrictions placed on the use of contrast agents (CAs) for noninvasive imaging modalities such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) affect the clinical management of these patients. With the goal to develop a next-generation CA for unfettered use for renal MRI, here we report, in a rodent model of chronic kidney disease, the preclinical safety and efficacy of a novel nanoparticle CA comprised of manganese (Mn2+) ions-intercalated graphene coated with dextran (hereafter called Mangradex). Nephrectomized rats received single or 5 times/week repeat (2 or 4 weeks) intravenous (IV) injections of Mangradex at two potential (low = 5 mg/kg, and high = 50 mg/kg) therapeutic doses. Histopathology results indicate that Mangradex does not elicit nephrogenic systemic fibrosis (NSF)-like indicators or questionable effects on vital organs of rodents. MRI at 7 Tesla magnetic field was performed on these rats immediately after IV injections of Mangradex at one potential therapeutic dose (25 mg/kg, [Mn2+] = 60 nmoles/kg) for 90 min. The results indicated significant (>100 %) and sustained contrast enhancement in the kidney and renal artery at these low paramagnetic ion (Mn2+) concentration; 2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose of long-circulating Gd3+-based MRI CA gadofosveset trisodium. The results open avenues for further development of Mangradex as an MRI CA to diagnose and monitor abnormalities in renal anatomy and vasculature.

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Acknowledgments

This work was supported by the Wallace H Coulter Foundation Translational Research Award, Fusion Award from the Stony Brook School of Medicine and the Office of the Vice President for Research, Technology Accelerator Fund from the Research Foundation for SUNY, and the National Institute of Health (1R41DK100205-01A1 and 2R44DK100205-02).

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    Authors and Affiliations

    1. Department of Biomedical Engineering, Northeastern University, Boston, MA, USA

      Shruti Kanakia, Jimmy Toussaint, Stephen Lee, Sayan Mullick Chowdhury, Slah Khan & Balaji Sitharaman

    2. Center for Translational Neuroimaging, Northeastern University, Boston, MA, USA

      Praveen Kukarni

    3. Division of Nephrology, Department of Medicine, Stony Brook University, Stony Brook, NY, USA

      Sandeep K. Mallipattu

    4. Department of Pathology, Stony Brook University, Bioengineering Bldg, Room 115, Stony Brook, NY, 11794-5281, USA

      Kenneth R. Shroyer

    5. Department of Radiology, Stony Brook University, Bioengineering Bldg, Room 115, Stony Brook, NY, 11794-5281, USA

      William Moore

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    1. Shruti Kanakia
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    Stony Brook University, along with its researchers, has filed patents related to the technology reported in this article. If licensing or commercialization occurs, the researchers are entitled to standard royalties. Balaji Sitharaman has financial interest in Theragnostic Technologies Inc., which, however, did not directly support this work.

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    Shruti Kanakia and Jimmy Toussaint have contributed equally to this work.

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    Kanakia, S., Toussaint, J., Kukarni, P. et al. Safety and efficacy of a high-performance graphene-based magnetic resonance imaging contrast agent for renal abnormalities. Graphene Technol 1, 17–28 (2016). https://doi.org/10.1007/s41127-016-0001-2

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