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Production and in vitro evaluation of no-carrier-added radio-cisplatin emitting Auger electrons
https://repo.qst.go.jp/records/83682
https://repo.qst.go.jp/records/83682b135dca1-fa34-413f-9bec-8b84d74747a1
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-10-07 | |||||
| タイトル | ||||||
| タイトル | Production and in vitro evaluation of no-carrier-added radio-cisplatin emitting Auger electrons | |||||
| 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 |
Honoka, Obata
× Honoka, Obata× Atsushi, Tsuji× Kotaro, Nagatsu× Mikako, Ogawa× Zhang, Ming-Rong× Honoka, Obata× Atsushi, Tsuji× Kotaro, Nagatsu× Mikako, Ogawa× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Aim/Introduction: Auger electrons (Auger e- ) have the potential for therapeutic applications by inducing nanoscale physiochemical damage to biomolecules due to their short-range (2-500 nm). Although DNA is the primary target of Auger e- , it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNAdamaging efect of Auger e- released as close as possible to DNA, we focused on a platinum(Pt)-based antineoplastic drug, cisplatin, because it can form direct DNA adducts between Pt and nucleobases. Here, to evaluate the efect of Auger e- without chemical factors we radio-synthesized nocarrier-added (n.c.a.) [189, 191Pt]cisplatin (radio-cisplatin), and investigated its in vitro properties and DNA-damaging efect in cultured cells. Materials and Methods: N.c.a. radio-cisplatin was radio-synthesized by treating n.c.a. radio-PtCl4 2- with excess NH3 and heating the reaction mixture, and the product was isolated by preparative HPLC. As in vitro evaluation of radio-cisplatin, cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofuorescence staining of γH2AX. Results: Our production method provided n.c.a. radio-cisplatin with a radiochemical purity of 99% at the end of synthesis. Although uptake of radio-cisplatin was low (0.6% incubated dose after 25-h incubation), approximately 20% of intracellular radio-Pt was in a nucleus, and 2% of intra-nucleus radio-Pt bound to DNA. Due to the low accumulation of radio-Pt, the frequency of cells with γH2AX foci was low (1%) in the γH2AX assays. Nevertheless, strong signals in nuclei of tumor cells treated with radio-cisplatin were found more often than with saline or nonradioactive cisplatin, suggesting Auger e- released very close to DNA cause more DSB. Conclusion: N.c.a. radio-cisplatin was successfully prepared at high radiochemical purities as an efective tool to evaluate DNA damage induced by Auger e- without chemical factors. Radio-cisplatin binding to DNA caused severe DSBs by the release of Auger e- very close to DNA without chemical damage by carriers. References: Obata, et al. Int. J. Mol. Sci. 2021, 22, 4622. Obata, et al. Sci Rep 2021, 11, 8140. |
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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 | EANM21(34th Annual Congress of the European Association of Nuclear Medicine) | |||||
| 発表年月日 | ||||||
| 日付 | 2021-10-20 | |||||
| 日付タイプ | Issued | |||||
