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64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics
https://repo.qst.go.jp/records/65683
https://repo.qst.go.jp/records/65683b204dd55-c97b-42e4-9198-c54530a4ca6a
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-06-18 | |||||
| タイトル | ||||||
| タイトル | 64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics | |||||
| 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 |
Yoshii, Yukie
× Yoshii, Yukie× Furukawa, Takako× Matsumoto, Hiroki× Yoshimoto, Mitsuyoshi× Zhang, Ming-Rong× Kiyono, Yasushi× Fujibayashi, Yasuhisa× Saga, Tsuneo× 吉井 幸恵× 古川 高子× 松本 博樹× 吉本 光喜× 張 明栄× 藤林 康久× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a promising theranostic agent targeting over-reduced condition under hypoxia in tumors. Clinical studies on diagnosis with radiolabeled Cu-ATSM are currently conducted worldwide, revealing its prognostic value. However, detailed characteristics of the region of high 64Cu-ATSM uptake remained unclear. Here, using human colon carcinoma HT-29 model, we investigated characteristics of 64Cu-ATSM uptake regions relating to tumor malignancy, such as up-regulation of DNA repair and concentration of CD133+ cancer stem cells, and developed a strategy to enhance 64Cu-ATSM internal radiotherapy efficacy by inhibiting DNA repair with co-administration of nucleic acid (NA) antagonists. Methods: Distribution of 64Cu-ATSM was examined in HT29 tumors, and the samples from regions identified as 64Cu-ATSM high- and low-uptake regions were used for characterization. Gene expression profile, NA incorporation (BrdU uptake), and CD133+ cell ratio were studied. For in vivo treatment study, 64Cu-ATSM (37 MBq) injection with or without co-administration of NA antagonists was tested and compared to 64Cu-ATSM alone (37 or 74 MBq). Results: Up-regulation of the pathways related to DNA repair along with BrdU uptake, and elevated CD133+ cell ratio were observed in 64Cu-ATSM high-uptake regions. In treatment study, 64Cu-ATSM showed dose-dependent inhibition of tumor growth, although 74 MBq showed significant toxicity. Co-administration of NA antagonists with 37 MBq 64Cu-ATSM showed greater tumor growth suppression than 74 MBq 64Cu-ATSM alone, without significant toxicity, and effectively reduced CD133+ cell ratio. Conclusions: 64Cu-ATSM accumulation was associated with tumor malignant characteristics and 64Cu-ATSM therapy with NA antagonists could be an effective approach to target these characteristics. | |||||
| 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 | The Society of Nuclear Medicine (SNM) annual meeting 2015 | |||||
| 発表年月日 | ||||||
| 日付 | 2015-06-09 | |||||
| 日付タイプ | Issued | |||||
