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Possibility of 123I-meta-iodobenzylguanidine (123I-MIBG) as companion diagnostic drug for therapeutic alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) in normal mice
https://repo.qst.go.jp/records/76187
https://repo.qst.go.jp/records/76187e44e3ebb-d95a-491a-bd63-fed7dd9b7bca
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-06-14 | |||||
| タイトル | ||||||
| タイトル | Possibility of 123I-meta-iodobenzylguanidine (123I-MIBG) as companion diagnostic drug for therapeutic 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 |
Yoshinaga, Keiichiro
× Yoshinaga, Keiichiro× Zhao, Songji× Washino, Komei× Aoki, Miho× Ken-ichi, Nishijima× Shimoyama, Saki× Ukon, Naoyuki× Tan, Chengbo× Washiyama, Kohshin× Takahashi, Kazuhiro× Ito, Hiroshi× Higashi, Tatsuya× Yoshinaga, Keiichiro× Washino, Komei× Higashi, Tatsuya |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abstract Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma, new effective approaches are being sought. The alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) has potential as a metastatic pheochromocytoma treatment. We previously reported the tumor volume reduction effects of 211At-MABG in a PC12 pheochromocytoma mouse model. As 211At-MABG does not emit gamma-rays suitable for dosimetry and imaging, 211At-MABG needs a companion diagnostic imaging agent such as 123I-meta-iodobenzylguanidine (123I-MIBG) to be used in making treatment decisions. However, the pharmacokinetics of 123I-MIBG as a companion drug for 211At-MABG radiotherapy have not been evaluated. The purpose of this study was to evaluate the similarities and differences between 123I-MIBG and 211At-MABG in biodistribution in normal mice under clinical conditions. Methods: In this biodistribution study, male normal mice (BALB/cCrSlc, 9 weeks old) received intravenously either 997kBq of the carrier-added commercial 123I-MIBG or 483kBq of the non-carrier-added 211At-MABG. 123I-MIBG dosage was calculated based on the human clinical dose for diagnostic imaging (111MBq/60kg) on a body surface area basis, and 211At-MABG dosage was the complete remission dose identified in a PC12-xenografted mouse model. The mice were sacrificed at 1 min, 30 min, 1 h, 3 h, 6 h, 12 h and 24 h after two tracer injections (n = 5 in each group). Blood, brain, thyroid, heart, lung, liver, spleen, stomach, small intestine, pancreas, kidney, adrenal gland, muscle, bone, urine and feces were collected, weighed and measured for radioactivity using a gamma counter. The biodistribution of two drugs was statistically compared at 6 hours post intravenous tracer injection which is the expected time to acquire images in clinical settings. Results: 211At-MABG and 123I-MIBG showed very similar biodistribution profiles in normal mice at every time point (see figure). Both drugs showed higher uptake in heart and adrenal glands. Specifically, at 6h, 123I-MIBG and 211At-MABG accumulation were similar in heart (15.5±1.5 vs. 18.1±2.8%ID/g, P=0.109) and adrenal gland (14.2±1.9 vs. 19.7±5.5%ID/g, P=0.067), respectively. 123I-MIBG showed lower uptake in lung (2.9±0.2 vs. 4.9±0.5%ID/g, P<0.0001) and liver (2.5±0.4 vs. 4.9±0.6%ID/g, P<0.0001) compared to 211At-MABG. In contrast, 123I-MIBG showed higher uptake in thyroid (0.53±0.21 vs. 0.20±0.07%ID, P=0.0090) than did 211At-MABG, suggesting that dehalogenation may occur more easily in 123I-MIBG than in 211At-MIBG. Total body excretion of 123I-MIBG at 24 h was higher than that of 211At-MABG (60.8±8.86% vs. 49.3±4.79%ID) (P=0.0328). Conclusions: At each time point, the trends for biodistribution of 123I-MIBG and 211At-MABG were almost similar in normal mice. A certain level of difference was observed in heart and adrenal gland, which have higher density of noradrenalin transporter compared to other organs. 123I-MIBG may be used for dosimetry and imaging for decisions regarding treatment with 211At-MABG radiotherapy as a companion drug. Where organs showed a difference in the estimated absorbed dose uptake of the two tracers, 123I-MIBG biodistribution data needs certain adjustments to compensate for possible under- or over-estimation of 211At-MABG absorbed dose. |
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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 | SNMMI 2019 Annual Meeting | |||||
| 発表年月日 | ||||||
| 日付 | 2019-06-25 | |||||
| 日付タイプ | Issued | |||||
