This SBIR phase 2 project focuses on preclinical investigational new drug (IND) enabling studies of a novel high performance carbon nanostructure-based magnetic resonance imaging (MRI) contrast agent (CA) to be used to diagnose and monitor patients with renal failure. Every year, in the US, approximately 20 million people are treated for mild to severe renal failure. A significant number of cases (greater than 30%) related to renal failure are at an advanced stage, and lead to incidences of morbidity, mortality and increase burden on health care resources and costs. Non-invasive imaging of renal injury or disease especially at advanced stages and /or other pathologies/ lesions in patients with renal failure is still a major challenge in clinic. X-ray computed tomography (CT) and MRI are routinely used in clinic to image the anatomy of kidneys and other organs. Exogenous chemicals called contrast agents (CAs) synthesized using the elements iodine and gadolinium has been widely employed to improve the diagnostic confidence of CT and MRI, respectively. However, in patients with advanced renal failure, these CAs have been linked to the onset of nephrotoxicity or the rare but potentially fatal disease nephrogenic systemic fibrosis (NSF). We have recently developed a novel carbon nanostructure-based MRI CA that comprises of high quality graphene (single sheet of graphite) nanoparticles (GNPs), intercalated (chemical species inserted and trapped in the voids between two graphene sheets), and coordinated with graphene trace amounts of manganese), and coated with natural biocompatible FDA-approved polymer dextran (hereafter called GNP-Dex). Our in vitro and in vivo (normal rats, and rat model of chronic kidney disease) safety and efficacy studies (pre-phase 1 and during phase 1) of this novel MRI CA showed good hemodynamic characteristics, increased in vivo circulation time (blood half-life of 1 hour), low acute toxicity (lethal dose LD5 value > 500 mg/kg), no chronic toxicity at therapeutic doses, no acute or chronic nephrotoxicity (including no NSF- like indicators), and greater contrast enhancement (~10 times greater) compared to clinical (Gd3+)-based MRI-CAs. These formed the basis of our recent request for an initial pre-IND meeting with the FDA (August 2013). Based on feedback from regulatory experts and FDA, the overall objective of SBIR phase 2 proposal is to scale up the manufacturing for GNP-Dex using GMPs practices for use in preclinical studies and to conduct of preclinical GLP safety and non- GLP efficacy studies in small and large animals. Successful completion of these aims will represent a critical step in accelerating the translation of this technology to the clinic; we anticipate that following completion of these aims, we will initiate te first-in-human trials. The final commercial product(s) will the first FDA-approved MRI CA for patients with renal failure. GNP-Dex will also prove useful as an alternative MRI CA to currently existing clinical first-pass and blood pool T1 MRI CAs.