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Biodistribution and safety evaluation of alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) in normal mice
https://repo.qst.go.jp/records/72889
https://repo.qst.go.jp/records/728894ecccaae-bb03-4c64-9730-308ee8f519ff
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-08-08 | |||||
| タイトル | ||||||
| タイトル | Biodistribution and safety evaluation of alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) 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_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 |
Sudo, Hitomi
× Sudo, Hitomi× Sugyo, Aya× Tsuji, Atsushi× Minegishi, Katsuyuki× Nagatsu, Kotaro× Ishioka, Noriko× Higashi, Tatsuya× Yoshinaga, Keiichiro× 須藤 仁美× 須尭 綾× 辻 厚至× 峯岸 克行× 永津 弘太郎× 石岡 典子× 東 達也× 吉永 恵一郎 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Therapeutic options for patients with malignant pheochromocytoma are currently limited. Therefore new treatment approaches are being sought. Alpha-emitting radiopharmaceutical meta-211At-astatobenzylguanidine (211At-MABG) has potential as a malignant pheochromocytoma treatment. We previously reported that 211At-MABG has a strong tumor volume-reduction effect in nude mice with pheochromocytoma. However, biodistribution and safety evaluation of 211At-MABG in normal mice have not been conducted. These investigations are important to developing 211At-MABG therapy for malignant pheochromocytoma. The purpose of this study was to evaluate the effects of 211At-MABG, especially with regard to safety aspects, on normal mice. Methods: In the biodistribution study, male mice (ICR, 6 weeks old) received 148 kBq of 211At-MABG intravenously. The mice were sacrificed at 1.5 min and 1, 3 and 24 h after injection (n = 5). Blood, brain, thyroid, heart, lung, liver, spleen, pancreas, stomach, small intestine, kidney, adrenal gland, muscle and bone were collected, weighed and measured for radioactivity using a gamma counter. In the safety evaluation, mice (body weight, 28.0 - 34.9 g) received 0 (saline as the control group), 1.1, 2.2, 3.3 and 4.4 MBq of 211At-MABG (n = 4 - 5) intravenously. We measured the body weight at least twice weekly until 4 weeks after injection. After euthanization, the brain, thyroid, heart, lung, liver, spleen, pancreas, stomach, intestine, kidney, adrenal glands, and bone were resected and weighed. Blood of mice injected with 3.3 MBq of 211At-MABG was collected from a tail vein, and hematologic indices (red and white blood cells, platelets, hemoglobin, hematocrit) were measured using a hematology analyzer. The data were analyzed by ANOVA with Dunnett's test. Results: 211At-MABG showed the highest uptake in the thyroid, followed by the stomach and the adrenal glands. Although the body weight of mice injected with 1.1 and 2.2 MBq of 211At-MABG decreased slightly and transiently, it recovered by day 5. The mice injected with 3.3 MBq of 211At-MABG showed significant body weight loss from day 3 to 5 (max. 16% loss; P < 0.05 vs. the control group), and their body weight increased subsequently and recovered by day 7. The mice injected with 4.4 MBq of 211At-MABG showed significant body weight loss, in excess of 20% at day 5 compared with that at day 0 (P < 0.01). They were therefore humanely euthanized. The adrenal gland weights of mice injected with 1.1, 2.2 and 3.3 MBq of 211At-MABG were significantly lower than those of the control group at day 28 (P < 0.05), whereas there were no significant differences in the other organs and blood cells. There were no other adverse effects such as diarrhea. Conclusions: The biodistribution of 211At-MABG in normal mice was almost consistent with that in nude mice as reported previously by our group. The dose of 4.4 MBq of 211At-MABG resulted in severe body weight loss while dosages of 3.3 MBq or less showed a transient loss. There was no significant difference in organ weight, other than for the adrenal glands, between the 211At-MABG treatment and control groups. These results suggest that the maximum tolerated dose with limited organ toxicity could be 3.3 MBq in normal mice. | |||||
| 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 | SNMMI2018 | |||||
| 発表年月日 | ||||||
| 日付 | 2018-06-24 | |||||
| 日付タイプ | Issued | |||||
