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Biodistribution and PET imaging study of 64Cu-anti-CTLA4 mAb in melanoma bearing mice
https://repo.qst.go.jp/records/66581
https://repo.qst.go.jp/records/66581fb6d85df-3938-46d8-b11b-63786b14fccc
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-01-10 | |||||
| タイトル | ||||||
| タイトル | Biodistribution and PET imaging study of 64Cu-anti-CTLA4 mAb in melanoma bearing 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 |
Jiang, Cuiping
× Jiang, Cuiping× Xie, Lin× Hanyu, Masayuki× Zhang, Yiding× Azuma, Rikako× Suzuki, Hisashi× Shimokawa, Takashi× Wakizaka, Hidekatsu× Zang, Shiming× Wang, Feng× Zhang, Ming-Rong× 謝 琳× 破入 正行× 張 一鼎× 東 梨佳子× 鈴木 寿× 下川 卓志× 脇坂 秀克× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose: Checkpoint blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) boosts anti-tumor T cell immunity and results in markedly clinical responses in diverse tumor types, including melanoma. Anti-CTLA4 monoclonal antibody (mAb) is the first immune checkpoint inhibitor approved by US Food and Drug Administration (FDA), but its in vivo action is still under investigation. Herein, to noninvasively track and quantify the distribution and action of anti-CTLA4 mAb, we developed 64Cu-anti-CTLA4 mAb ( [64Cu]1) as a novel radiotracer to investigate its pharmacokinetics in the whole bodies of mice. Method: [64Cu]1 was synthesized by labeling DOTA-anti-CTLA4 mAb with 64Cu. Biodistribution and small-animal PET scans were performed at 1 h, 24 h, 48 h, 72 h after [64Cu]1 injection into immunocompetent C57BL/6 mice bearing B16F10 melanoma. Result: [64Cu]1 carried through the blood (28.1 % ID/g) to heart (4.7 % ID/g), lung (6.2 % ID/g), and kidney (7.5 % ID/g) at 1 h after injection, followed by a rapid distribution throughout the whole body. Sustained high radioactivity accumulated in the liver from 1 h (18.3 % ID/g) to 48 h (13.9 % ID/g) after [64Cu]1 injection. The lowest radioactivity was found in the muscle (0.7 % ID/g) and brain (0.8 % ID/g). For the immune organs, [64Cu]1 achieved excellent penetration in gut-associated lymphoid tissue (GALT), reached the highest uptake at 1 h (7.7 % ID/g), 24 h (93.3 % ID/g, 48 h (44.6 % ID/g), higher uptake in spleen at 1 h (17.8 % ID/g), 24 h (17.4 % ID/g), 48 h (12.7 % ID/g), relatively constant uptake in thymus (1.5-2.4 % ID/g). In B16F10 tumors, high accumulation of anti-CTLA4 mAb was shown at 24 h (7.3 % ID/g) and retention at 48 h (5.4 % ID/g). At 72 h after injection, [64Cu]1 was rem oved by hepatobiliary and renal clearance, generating a low radioactivity in the liver (4.3 % ID/g), intestine (1.0 % ID/g) and kidney (3.9 % ID/g), with background radioactivity in the other organs (1.1-5.4 % ID/g). The three-dimensional PET imaging confirmed the biodistribution pattern of [64Cu]1, supporting digital reconstruction and quantification of its pharmacokinetics in spleen, GALT, B16F10 tumors and other organs and tissue in a noninvasive and temporal-spatial pattern. Conclusion: This study determined the pharmacokinetics of CTLA4 mAb in mice bearing melanoma, which would be helpful for facilitating the development of anti-CTLA4 mAb immunotherapy. |
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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 | Japan-China Nuclear Medicine Exchange Meeting | |||||
| 発表年月日 | ||||||
| 日付 | 2017-10-07 | |||||
| 日付タイプ | Issued | |||||
