WEKO3
アイテム
小細胞肺癌におけるc-kit 特異的イメージングプローブの開発
https://repo.qst.go.jp/records/70083
https://repo.qst.go.jp/records/70083679e0602-e54a-4795-a01c-bac4780a94db
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-04-20 | |||||
| タイトル | ||||||
| タイトル | 小細胞肺癌におけるc-kit 特異的イメージングプローブの開発 | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 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 |
吉田, 千里
× 吉田, 千里× 吉田 千里 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | C-kit is a 145kDa transmembrane glycoprotein and a tyrosine kinase type receptor for the stem cell factor. C-kit is well known to be a protooncogene, and mutations of this gene induce ligand-independent tyrosine kinase activation and autophosphorylation, which leads to uncontrolled cell proliferation and carcinogenesis. C-kit is highly expressed in gastrointestinal stromal tumors (GISTs), small cell lung cancer (SCLC), etc. SCLC, representing about 20% of all lung cancer types, is an aggressive form of lung cancers, and tends to develop metastases to lymph nodes and other organs at an early stage. The overall prognosis remains poor, though SCLC is sensitive to chemotherapy and radiation. Imatinib, a specific inhibitor of c-kit-tyrosine kinase, has been found to be highly effective against the chemotherapy-resistant GISTs and may be applicable for SCLC. Because not all SCLC express c-kit, we need a c-kit-specific imaging method to select SCLC patients who will respond to imatinib treatment and to broaden treatment options. In this study, we labeled anti-c-kit antibodies (IgG and Fab) with 125I, 111In and 64Cu, and assessed the in vitro and in vivo characteristics. Methods; We labeled murine anti-c-kit antibodies with 125I using a chloramine-T, 111In using a CHX-A"-DTPA and 64Cu using a p-Bn-DOTA, and performed cell binding, competitive inhibition and internalization assays using a human SCLC cell line, SY, expressing c-kit. We also performed biodistribution, PET and SPECT imaging using mice bearing SY tumors. Results: Cell binding and competitive inhibition assays showed that radiolabeled antibodies retained immunoreactivity to c-kit and specifically bound to SY cells. Internalization assay showed that IgG was quickly internalized into cells, while Fab was slowly internalized. Biodistribution experiments showed that tumor uptake of 111In-IgG were 15.5+/-1.9, 23.3+/-2.3 and 20.3+/-1.6 %ID/g after 24, 48 and 96h, respectively, and those of 64Cu-Fab were 2.6+/-0.7, 6.1+/-0.2 and 6.2+/-2.0 %ID/g after 1, 6 and 12h respectively. In contrast, tumor uptake of 125I-labeled IgG and Fab remained low and decreased with time, probably because of the internalization and dehalogenation of 125I-labeled antibodies, suggesting that labeling with metal radionucleotide is suitable for imaging. In fact, we got clear planar and SPECT images of xenografted tumors at day 4 after injection of 111In-IgG, and PET images at 6h after injection of 64Cu-Fab. Conclusion: 111In-IgG and 64Cu-Fab used in this study would be useful for SPECT or PET imaging of c-kit expression in SCLC. | |||||
| 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 | 分子イメージング研究シンポジウム２０１０ | |||||
| 発表年月日 | ||||||
| 日付 | 2010-01-22 | |||||
| 日付タイプ | Issued | |||||
