title: Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1.
abstract: OBJECTIVE
  Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes.
  
  
  METHODS
  Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of (123)I-GLP-1 or (123)I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using (125)I-GLP-1 or (125)I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured.
  
  
  RESULTS
  In the noninvasive imaging studies, a relatively high accumulation level of (123)I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of (123)I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of (123)I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using (125)I-labeled peptides. The AUC of (125)I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1.
  
  
  CONCLUSIONS
  This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals.
authors.affiliation: Department of Radiobiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ayahisa
authors.initials: A
authors.lastname: Watanabe
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemoto
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D006031:Glycosylation; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D052216:Glucagon-Like Peptide 1