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Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent 211At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice
https://repo.qst.go.jp/records/75787
https://repo.qst.go.jp/records/75787afbbe31c-7895-44d0-8ff9-7eab61985afb
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-05-10 | |||||
| タイトル | ||||||
| タイトル | Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent 211At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice | |||||
| 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 |
Sudo, Hitomi
× Sudo, Hitomi× Tsuji, Atsushi× Sugyo, Aya× Nagatsu, Kotaro× Minegishi, Katsuyuki× Ishioka, Noriko× Ito, Hiroshi× Yoshinaga, Keiichiro× Higashi, Tatsuya× Sudo, Hitomi× Tsuji, Atsushi× Sugyo, Aya× Nagatsu, Kotaro× Minegishi, Katsuyuki× Ishioka, Noriko× Ito, Hiroshi× Yoshinaga, Keiichiro× Higashi, Tatsuya |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The α-emitter 211At-labeled meta-astatobenzylguanidine (211At-MABG) has a strong antitumor effect on pheochromocytoma xenograft tumors and holds great promise as a new therapeutic option for malignant pheochromocytoma. To evaluate the acute radiation-related toxicity of 211At-MABG, we conducted biodistribution and dosimetry studies of 211At-MABG in ICR mice to estimate the doses absorbed by organs. We determined the maximum tolerated doses (MTD) of 211At-MABG on the basis of body weight loss and assessed the acute radiation-related toxicity induced by MTD administration on the basis of organ weights, histologic features, hematologic indices, and biochemical indices. The biodistribution and dosimetry studies of α-emitting 211At-MABG revealed high doses absorbed by most organs except the brain in ICR mice. The administration of 1.1, 2.2, and 3.3 MBq of 211At-MABG induced transient body weight loss, and 4.4 MBq of 211At-MABG induced unrecoverable body weight loss; thus, the MTD was 3.3 MBq for ICR mice. Although by day 5 the administration of 3.3 MBq had induced some radiation-related toxicity symptoms—such as body weight loss and leucopenia, which are generally observed in radiation therapy including β−-emitting radiopharmaceuticals—the mice had recovered by day 28. We observed no unexpected severe toxicity in ICR mice despite the high absorbed doses in most organs, especially the thyroid, heart, stomach, and adrenal glands. Our findings suggest that therapeutic treatments with appropriate doses of 211At-MABG estimated by dosimetry in each patient could be tolerated, although lower doses may initially be necessary to ensure patient safety in the first-in-human study. | |||||
| 書誌情報 |
Translational Oncology 巻 12, 号 7, p. 879-888, 発行日 2019-07 |
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| 出版者 | ||||||
| 出版者 | ELSEVIER | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1936-5233 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.tranon.2019.04.008 | |||||
| 関連サイト | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.tranon.2019.04.008 | |||||
