WEKO3
アイテム
Alkyl-fluorinated thymidine derivatives for imaging cell proliferation - I. The <i>in vitro </i>evaluation of some alkyl-fluorinated thymidine derivatives.
https://repo.qst.go.jp/records/68389
https://repo.qst.go.jp/records/68389b13899a5-e43d-46b5-9c9e-aba182611c30
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-06-12 | |||||
| タイトル | ||||||
| タイトル | Alkyl-fluorinated thymidine derivatives for imaging cell proliferation - I. The <i>in vitro </i>evaluation of some alkyl-fluorinated thymidine derivatives. | |||||
| 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 |
Toyohara, Jun
× Toyohara, Jun× Hayashi, Akio× Gogami, Akie× Kato, Takahiro× Node, Manabu× Fujibayashi, Yasuhisa× 豊原 潤 |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Derivatives of 2'-deoxyuridine that contains fluoroalkyl groups at the C5 position and derivatives of thymidine that contains fluoroalkyl groups at the N3 position were synthesized and examined in three in vitro assays designed to evaluate their potential as a radiopharmaceuticals for imaging cellular proliferation. Methods: 5-(2-fluoroethyl)-,5-(fluoromethyl)-4'-thio-,and 5-(2-fluoroethyl)-4'-thio-derivatives of 2'-deoxyuridine were synthesized as C5 alkyl-fluorinated derivatives. N8-(Fluoromethyl)-,N8-(2-fluoroethyl)-,N8-(3-fluoropropyl)-,and N8-(2-fluoroethyl)-4'-thio-derivatives of thymidine were synthesized as N3 alkyl-fluorinated derivatives. 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-N8-(2-fluoroethyl)-thymine was also synthesized as N3 alkyl-fluorinated derivatives. We have compared the in vitro phosphorylation rates of these nucleosides by phosphoryl-transfer assay with recombinant human thymidne kinase 1 (TK1). The nucleoside transport inhibition constant (Ki) were measured to evaluate their interaction with the nucleoside transporter. Their stability toward the phosphorolytic enzyme thymidne phosphorylase (an enzyme that catalyzes the glycosidic bond of thymidine and 2'-deoxyuridine derivatives) has been used as an indicator of their metabolic stability. Results: The phosphoryl-transfer assay showed that all three of the C5 alkyl-fluorinated derivatives and four of the N3 alkyl-fluorinated ones were phosphorylated by recombinant human TK1, and that N8-(2-fluoroethyl)-thymidine (NFT202) is the most potent substrate of the eight nucleosides studied. The transport assay indicated that all eight nucleosides have good affinity for an NBMPR-sensitive mouse erythrocyte nucleoside transporter, with inhibition constants in the range of 0.02-0.55 mM. The degradation assay showed that one of the C5 alkyl-fluorinated derivatives and all five of the N3 alkyl-fluorinated ones were not degraded by recombinant E. coli thymidine phosphorylase. Conclusions: From these in vitro screening assays, we selected NFT202 as a candidate for subsequent in vivo evaluation, because this compound met the three basic criteria of the in vitro screening assays and had the most potent phosphorylation activity as a substrate for recombinant human TK1. In addition, this compound might be amenable to labeling with 18F by the use of a known method. Further investigation of the feasibility of 18F-lableled NFT202 as a cell proliferation marker is needed. |
|||||
| 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 | 53ｒｄ Annual Meeting | |||||
| 発表年月日 | ||||||
| 日付 | 2006-06-07 | |||||
| 日付タイプ | Issued | |||||
