WEKO3
アイテム
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To assess the DNAdamaging efect of Auger e-\n released as close as possible \nto DNA, we focused on a platinum(Pt)-based antineoplastic \ndrug, cisplatin, because it can form direct DNA adducts \nbetween Pt and nucleobases. Here, to evaluate the efect of \nAuger e-\n without chemical factors we radio-synthesized nocarrier-added (n.c.a.) [189, 191Pt]cisplatin (radio-cisplatin), and \ninvestigated its in vitro properties and DNA-damaging efect \nin cultured cells. Materials and Methods: N.c.a. radio-cisplatin \nwas radio-synthesized by treating n.c.a. radio-PtCl4\n2- with \nexcess NH3\n and heating the reaction mixture, and the product \nwas isolated by preparative HPLC. As in vitro evaluation of \nradio-cisplatin, cellular uptake, intracellular distribution, and \nDNA binding were investigated, and DNA double-strand \nbreaks (DSBs) were evaluated by immunofuorescence \nstaining of γH2AX. Results: Our production method provided \nn.c.a. radio-cisplatin with a radiochemical purity of 99% at the \nend of synthesis. Although uptake of radio-cisplatin was low \n(0.6% incubated dose after 25-h incubation), approximately \n20% of intracellular radio-Pt was in a nucleus, and 2% \nof intra-nucleus radio-Pt bound to DNA. Due to the low \naccumulation of radio-Pt, the frequency of cells with γH2AX \nfoci was low (1%) in the γH2AX assays. Nevertheless, strong \nsignals in nuclei of tumor cells treated with radio-cisplatin \nwere found more often than with saline or nonradioactive \ncisplatin, suggesting Auger e-\n released very close to DNA \ncause more DSB. Conclusion: N.c.a. radio-cisplatin was \nsuccessfully prepared at high radiochemical purities as an \nefective tool to evaluate DNA damage induced by Auger \ne-\n without chemical factors. Radio-cisplatin binding to DNA \ncaused severe DSBs by the release of Auger e-\n very close \nto DNA without chemical damage by carriers. References:\nObata, et al. Int. J. Mol. Sci. 2021, 22, 4622. Obata, et al. 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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 |