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Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1
| Title: | Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 |
| Authors: | Watanabe, Ayahisa Browse this author | | Nishijima, Ken-ichi Browse this author | | Zhao, Songji Browse this author | | Tanaka, Yoshikazu Browse this author | | Itoh, Takeshi Browse this author | | Takemoto, Hiroshi Browse this author | | Tamaki, Nagara Browse this author | | Kuge, Yuji Browse this author |
| Keywords: | Noninvasive imaging | | Biodistribution | | Glycosylation | | Glucagon-like peptide 1 |
| Issue Date: | Feb-2012 |
| Publisher: | Springer Japan |
| Journal Title: | Annals of Nuclear Medicine |
| Volume: | 26 |
| Issue: | 2 |
| Start Page: | 184 |
| End Page: | 191 |
| Publisher DOI: | 10.1007/s12149-011-0558-z |
| PMID: | 22187312 |
| 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. |
| Rights: | The original publication is available at www.springerlink.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/48646 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 渡邊 郁剛
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