title: Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics.
abstract: Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity.
  
  
  BACKGROUND
  In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.
authors.affiliation: Nanoscience and Nanotechnology Research Center, Research Organization for 21st Century, Osaka Prefecture University, Osaka, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kojima
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Celeste A S
authors.initials: CA
authors.lastname: Regino
authors.forename: L Henry
authors.initials: LH
authors.lastname: Bryant
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Kenji
authors.initials: K
authors.lastname: Kono
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D011092:Polyethylene Glycols; D005682:Gadolinium