title: Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals.
abstract: Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Kanakia
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Toussaint
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY USA.
authors.forename: Dung Minh
authors.initials: DM
authors.lastname: Hoang
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
authors.forename: Sayan
authors.initials: S
authors.lastname: Mullick Chowdhury
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
authors.affiliation: Department of Radiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: William
authors.initials: W
authors.lastname: Moore
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY USA.
authors.forename: Youssef Z
authors.initials: YZ
authors.lastname: Wadghiri
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Sitharaman
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005682:Gadolinium / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006108:Graphite / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D008345:Manganese; D006108:Graphite; D005682:Gadolinium