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Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors.
https://repo.qst.go.jp/records/45107
https://repo.qst.go.jp/records/4510720092b18-a60c-43a2-81d9-f155fefabb60
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-03-04 | |||||
| タイトル | ||||||
| タイトル | Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hanaoka, Hirofumi
× Hanaoka, Hirofumi× Mukai, Takahiro× Habashita, Sayo× Asano, Daigo× Ogawa, Kazuma× Kuroda, Yoshihiro× Akizawa, Hiromichi× IIda, Yasuhiko× Endou, Keigo× Saga, Tsuneo× Saji, Hideo× 秋澤 宏行× 遠藤 啓吾× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo. | |||||
| 書誌情報 |
Nuclear Medicine and Biology 巻 34, 号 5, p. 503-510, 発行日 2007-07 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
