open access

https://hdl.handle.net/2115/48646

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

英語

Glucagon-like peptide 1

2012-02

Springer Japan

Annals of Nuclear Medicine

26(2)

184-191

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.

学術雑誌論文

Accepted Manuscript

The original publication is available at www.springerlink.com

0914-7187