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ファイル | 記述 | サイズ | フォーマット | |
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j.bmc.2021.116496.pdf | 1.08 MB | Adobe PDF | 見る/開く |
タイトル: | Development of novel radioiodinated exendin-4 derivatives targeting GLP-1 receptor for detection of β-cell mass |
著者: | Ogawa, Yu Kimura, Hiroyuki Fujimoto, Hiroyuki https://orcid.org/0009-0009-7084-1423 (unconfirmed) Kawashima, Hidekazu Toyoda, Kentaro Mukai, Eri Yagi, Yusuke Ono, Masahiro https://orcid.org/0000-0002-2497-039X (unconfirmed) Inagaki, Nobuya Saji, Hideo |
著者名の別形: | 小川, 祐 木村, 寛之 藤本, 裕之 河嶋, 秀和 豊田, 健太郎 向, 英里 屋木, 祐亮 小野 正博 稲垣, 暢也 佐治, 英郎 |
キーワード: | Glucagon-like peptide-1 receptor Exendin-4 β-cell imaging probe ¹²³I |
発行日: | 15-Dec-2021 |
出版者: | Elsevier BV |
誌名: | Bioorganic & Medicinal Chemistry |
巻: | 52 |
論文番号: | 116496 |
抄録: | In subjects with type 2 diabetes mellitus (T2DM), pancreatic β-cell mass decreases; however, it is unknown to what extent this decrease contributes to the pathophysiology of T2DM. Therefore, the development of a method for noninvasive detection of β-cell mass is underway. We previously reported that glucagon-like peptide-1 receptor (GLP-1R) is a promising target molecule for β-cell imaging. In this study, we attempted to develop a probe targeting GLP-1R for β-cell imaging using single-photon emission computed tomography (SPECT). For this purpose, we selected exendin-4 as the lead compound and radiolabeled lysine at residue 12 in exendin-4 or additional lysine at the C-terminus using [¹²³I]iodobenzoylation. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Biodistribution study was performed in normal ddY mice. Ex vivo autoradiography was performed in transgenic mice expressing green fluorescent protein under control of the mouse insulin I gene promoter. Additionally, SPECT imaging was performed in normal ddY mice. The affinity of novel synthesized derivatives toward pancreatic β-cells was not affected by iodobenzoylation. The derivatives accumulated in the pancreas after intravenous administration specifically via GLP-1R expressed on the pancreatic β-cells. Extremely high signal-to-noise ratio was observed during evaluation of biodistribution of [¹²³I]IB12-Ex4. SPECT images using normal mice showed that [¹²³I]IB12-Ex4 accumulated in the pancreas with high contrast between the pancreas and background. These results indicate that [123I]IB12-Ex4 for SPECT is useful for clinical applications because of its preferable kinetics in vivo. |
著作権等: | © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ The full-text file will be made open to the public on 15 December 2023 in accordance with publisher's 'Terms and Conditions for Self-Archiving' This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/266599 |
DOI(出版社版): | 10.1016/j.bmc.2021.116496 |
PubMed ID: | 34808404 |
出現コレクション: | 学術雑誌掲載論文等 |
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