title: Cellular delivery of MRI contrast agents.
abstract: Magnetic resonance imaging (MRI) is a powerful tool for acquiring images of opaque living animals with the benefit of tracking events over extended periods of time on the same specimen. Contrast agents are used to enhance regions, tissues, and cells that are magnetically similar but histologically distinct. A principal barrier to the development of MRI contrast agents for investigating biological questions is the delivery of agents across cellular membranes. Here, we describe the synthesis and in vitro testing of Gd(III)-based MRI contrast agents containing varying length polyarginine oligomers capable of permeating cell membranes. We examine the effect of the length of oligomer on T(1) enhancement and cellular uptake. Furthermore, the effect of incubation time, concentration, and cell type on uptake is explored. Toxicity and washout studies are performed in addition to MRI phantom studies.
authors.affiliation: Departments of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Allen
authors.forename: Keith W
authors.initials: KW
authors.lastname: MacRenaris
authors.forename: P N
authors.initials: PN
authors.lastname: Venkatasubramanian
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D000442:Octanols / Q000737:chemistry; D051381:Rats; D014867:Water / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D028581:Lanthanoid Series Elements; D000442:Octanols; D014867:Water; D001120:Arginine