title: Toxicity, biodistribution, and ex vivo MRI detection of intravenously injected cationized ferritin.
abstract: The goal of the work was to establish the toxicity and biodistribution of the superparamagnetic protein cationized ferritin (CF) after intravenous injection. Intravenously injected CF has been used to target the extracellular matrix with high specificity in the kidney glomerulus, allowing measurements of individual glomeruli using T2*-weighted MRI. For the routine use of CF as an extracellular matrix-specific tracer, it is important to determine whether CF is toxic. In this work, we investigated the renal and hepatic toxicity, leukocyte count, and clearance of intravenously injected CF. Furthermore, we studied CF labeling in several organs using MRI and immunohistochemistry. Serum measurements of biomarkers suggest that intravenous injection of CF is neither nephrotoxic nor hepatotoxic and does not increase leukocyte counts in healthy rats at a dose of 5.75 mg/100 g. In addition to known glomerular labeling, confocal and MRI suggest that intravenously injected CF labels the extracellular matrix of the hepatic sinusoid, extracellular glycocalyx of alveolar endothelial cells, and macrophages in the spleen. Liver T2* values suggest that CF is cleared by 7 days after injection. These results suggest that CF may serve as a useful contrast agent for detection of a number of structures and functions with minimal toxicity.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Beeman
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Georges
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Bennett
mesh_terms: D000818:Animals; D002412:Cations; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D005293:Ferritins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D002412:Cations; D003287:Contrast Media; D005293:Ferritins