title: Synthesis and characterization of a Gd-DOTA-D-permeation peptide for magnetic resonance relaxation enhancement of intracellular targets.
abstract: Many MR contrast agents have been developed and proven effective for extracellular nontargeted applications, but exploitation of intracellular MR contrast agents has been elusive due to the permeability barrier of the plasma membrane. Peptide transduction domains can circumvent this permeability barrier and deliver cargo molecules to the cell interior. Based upon enhanced cellular uptake of permeation peptides with D-amino acid residues, an all-D Tat basic domain peptide was conjugated to DOTA and chelated to gadolinium. Gd-DOTA-D-Tat peptide in serum at room temperature showed a relaxivity of 7.94 +/- 0.11 mM(-1) sec(-1) at 4.7 T. The peptide complex displayed no significant binding to serum proteins, was efficiently internalized by human Jurkat leukemia cells resulting in intracellular T1 relaxation enhancement, and in preliminary T1-weighted MRI experiments, significantly enhanced liver, kidney, and mesenteric signals.
authors.affiliation: Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prantner
authors.forename: Vijay
authors.initials: V
authors.lastname: Sharma
authors.forename: Joel R
authors.initials: JR
authors.lastname: Garbow
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D015696:Gene Products, tat / Q000138:chemical synthesis* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008643:Mesentery / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D002614:Chelating Agents; D003287:Contrast Media; C482383:Gd-DOTA-D-TAT peptide; D015696:Gene Products, tat; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010455:Peptides; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate