Safety and efficacy of a high-performance graphene-based magnetic resonance imaging contrast agent for renal abnormalities
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.
KeywordsNephrogenic systemic fibrosis Gadolinium Mangradex Chronic kidney disease Contrast agent Magnetic resonance imaging
|Funder Name||Grant Number||Funding Note|
|National Institutes of Health|
|Wallace H. Coulter Foundation|