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01-02-2012 | Original article

Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

Authors: Ayahisa Watanabe, Ken-ichi Nishijima, Songji Zhao, Yoshikazu Tanaka, Takeshi Itoh, Hiroshi Takemoto, Nagara Tamaki, Yuji Kuge

Published in: Annals of Nuclear Medicine | Issue 2/2012

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 ¹²³I-GLP-1 or ¹²³I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using ¹²⁵I-GLP-1 or ¹²⁵I-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 ¹²³I-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 ¹²³I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of ¹²³I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using ¹²⁵I-labeled peptides. The AUC of ¹²⁵I-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.

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Title: Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1
Authors: Ayahisa Watanabe
Ken-ichi Nishijima
Songji Zhao
Yoshikazu Tanaka
Takeshi Itoh
Hiroshi Takemoto
Nagara Tamaki
Yuji Kuge
Publication date: 01-02-2012
Publisher: Springer Japan
Published in: Annals of Nuclear Medicine / Issue 2/2012
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI: https://doi.org/10.1007/s12149-011-0558-z

At a glance: The STEP trials

Springer Medicine

Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

Abstract

Objective

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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