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Evaluation of Aminopolycarboxylate Chelators for Whole-Body Clearance of Free Ac: A Feasibility Study to Reduce Unexpected Radiation Exposure during Targeted Alpha Therapy.
https://repo.qst.go.jp/records/85105
https://repo.qst.go.jp/records/85105a47339e0-505a-4a61-aa1c-d337d8616d2c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-10-12 | |||||
| タイトル | ||||||
| タイトル | Evaluation of Aminopolycarboxylate Chelators for Whole-Body Clearance of Free Ac: A Feasibility Study to Reduce Unexpected Radiation Exposure during Targeted Alpha Therapy. | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Yoshimoto, Mitsuyoshi
× Yoshimoto, Mitsuyoshi× Yoshii, Yukie× Matsumoto, Hiroki× Shinada, Mitsuhiro× Takahashi, Masashi× Igarashi, Chika× Hihara, Fukiko× Tachibana, Tomoko× Doi, Ayano× Higashi, Tatsuya× Fujii, Hirofumi× Washiyama, Kohshin× Mitsuyoshi, Yoshimoto× Yukie, Yoshii× Hiroki, Matsumoto× Mitsuhiro, Shinada× Masashi, Takahashi× Chika, Igarashi× Fukiko, Hihara× Tomoko, Tachibana× Tatsuya, Higashi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Actinium-225 (Ac) is a promising radionuclide used in targeted alpha therapy (TAT). Although Ac labeling of bifunctional chelating ligands is effective, previous in vivo studies reported that free Ac can be released from the drugs and that such free Ac is predominantly accumulated in the liver and could cause unexpected toxicity. To accelerate the clinical development of Ac TAT with a variety of drugs, preparing methods to deal with any unexpected toxicity would be valuable. The aim of this study was to evaluate the feasibility of various chelators for reducing and excreting free Ac and compare their chemical structures. Nine candidate chelators (D-penicillamine, dimercaprol, Ca-DTPA, Ca-EDTA, CyDTA, GEDTA TTHA, Ca-TTHA, and DO3A) were evaluated in vitro and in vivo. The biodistribution and dosimetry of free Ac were examined in mice before an in vivo chelating study. The liver exhibited pronounced Ac uptake, with an estimated human absorbed dose of 4.76 Sv/MBq. Aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, significantly reduced Ac retention in the liver (22% and 30%, respectively). Significant Ac reductions were observed in the heart and remainder of the body with both Ca-DTPA and Ca-TTHA, and in the lung, kidney, and spleen with Ca-TTHA. In vitro interaction analysis supported the in vivo reduction ability of Ca-DTPA and Ca-TTHA. In conclusion, aminopolycarboxylate chelators with five and six carboxylic groups, Ca-DTPA and Ca-TTHA, were effective for whole-body clearance of free Ac. This feasibility study provides useful information for reducing undesirable radiation exposure from free Ac. | |||||
| 書誌情報 |
Pharmaceutics 巻 13, 号 10, p. 1706, 発行日 2021-10 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1999-4923 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 34683999 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3390/pharmaceutics13101706 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.mdpi.com/1999-4923/13/10/1706 | |||||
