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The Src-homology 2 (SH2) domain of growth factor receptor bound protein 2 (Grb2) has a potential for in vivo imaging, targeting activated epidermal growth factor receptor (EGFR)
https://repo.qst.go.jp/records/69863
https://repo.qst.go.jp/records/69863e2ac481c-9f80-4684-8632-aa81a1fdc42c
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-09-29 | |||||
| タイトル | ||||||
| タイトル | The Src-homology 2 (SH2) domain of growth factor receptor bound protein 2 (Grb2) has a potential for in vivo imaging, targeting activated epidermal growth factor receptor (EGFR) | |||||
| 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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 |
Saito, Yuriko
× Saito, Yuriko× Furukawa, Takako× Arano, Yasushi× Fujibayashi, Yasuhisa× Saga, Tsuneo× 齋藤 有里子× 古川 高子× 荒野 泰× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abnormal activation of EGFR is known to be involved in cancer pathogenesis and its malignancy. In order to generate an imaging probe that can capture EGFR activation, not the amount or structure of EGFR, we designed a new protein probe. We selected SH2 domain of Grb2, an adaptor protein of activated-EGFR, for the key component of the probe, and added transactivating transduction (TAT), flag and tyrosine residue, for protein transduction into cells, molecular analysis and radiolabeling, respectively, to produce a probe protein named TSF. Having confirmed that TSF can cross the cell membrane and bind to EGFR, we moved to examine the efficacy of TSF in vivo by labeling it with 125I. Labeling efficiency of 125I-TSF by chloramine-T method was about 40 % and average of 0.8 molecule of 125I was calculated to be on single TSF molecule. After column purification, the radiochemical purity was more than 99 %. The amount of 125I-TSF taken up into cells was significantly higher in EGFR positive A431 cells (24.6+/-3.7%) than EGFR negative MDA-MB435 cells (20.4+/-2.1%). When the biodistribution of 125I-TSF was examined in tumor-bearing mice at 0.5, 1, and 3 h after the administration from the tail vein, the radioactivity in A431 tumor was increased for 1 h after the administration, while that into the other tissues including MDA-MB435 tumor was decreased over time. A431 tumor-to-tissue ratio was highest at 1 h after injection, and A431 tumor accumulated 1.6-fold more TSF than MDA-MB435 tumor. A431 tumor-to-blood and -muscle ratios were 1.1 and 3.5, respectively. However, high accumulation of the radioactivity in stomach indicated rapid de-iodination of the labeled probe in vivo. In conclusion, SH2 domain of Grb2 has a potential as a key component of the probe to detect EGFR activation in vivo, though direct 125I-labeling would not be suitable. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | World Molecular Imaging Congress | |||||
| 発表年月日 | ||||||
| 日付 | 2009-09-26 | |||||
| 日付タイプ | Issued | |||||
