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Toward in Vivo Imaging of Heart Disease Using a Radiolabeled Single-Chain Fv Fragment Targeting Tenascin-C
https://repo.qst.go.jp/records/46288
https://repo.qst.go.jp/records/462883c070357-f9b5-4aaa-b088-e1ebf75bb7cd
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-03-21 | |||||
| タイトル | ||||||
| タイトル | Toward in Vivo Imaging of Heart Disease Using a Radiolabeled Single-Chain Fv Fragment Targeting Tenascin-C | |||||
| 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 |
Kobayashi, Norihiro
× Kobayashi, Norihiro× Odaka, Kenichi× Uehara, Tomoya× Yoshida, Kyoko× Ohyama, Hiroyuki× Tadokoro, Hiroyuki× Hiroe, Michiaki× Fukumura, Toshimitsu× Komuro, Issei× Arano, Yasushi× 小高 謙一× 上原 知也× 田所 裕之× 福村 利光× 荒野 泰 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Antibodies specific to a particular target molecule can be used as analytical reagents, not only for in vitro immunoassays but also for noninvasive in vivo imaging, e.g., immunoscintigraphies. In the latter case, it is important to reduce the size of antibody molecules in order to achieve suitable in vivo "diagnostic kinetics" and generate higher-resolution images. For these purposes, single-chain Fv fragments (scFvs; Mr < 30 kDa) have greater potential than intact immunoglobulins (150 kDa) or Fab (or Fab') fragments (50 kDa). Our recent observation of enhanced tenascin-C (Tnc) expression at sites of cardiac repair after myocardial infarction prompted us to develop a radiolabeled scFv against Tnc for in vivo imaging of heart disease. We cloned the genes encoding the heavy and light chain variable domains of the mouse anti-Tnc monoclonal antibody 4F10, and combined them to create a single gene. The resulting scFv-4F10 gene was expressed in E. coli cells to produce soluble scFv proteins. scFv-4F10 has an affinity for Tnc (Ka = 3.5X107 M–1), similar to the Fab fragment of antibody 4F10 (Ka = 1.3X107 M–1) and high enough to be of practical use. A cysteine residue was then added to the C-terminus to achieve site-specific 111In labeling via a chelating group. The resulting 111In-labeled scFv was administered to a rat model of acute myocardial infarction. Biodistribution and quantitative autoradiographic studies indicated higher uptake of the radioactivity at the infarcted myocardium than the noninfarcted one. Single photon emission computed tomography (SPECT) provided in vivo cardiac images that coincided with the ex vivo observations. Our results will promote advances in diagnostic strategies for heart disease. | |||||
| 書誌情報 |
Analytical Chemistry 巻 83, 号 23, p. 9123-9130, 発行日 2011-11 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0003-2700 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/ac202159p | |||||
