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Theranostics of melanoma targeting metabotropic glutamate receptor 1 with a novel small-molecular radiopharmaceutical pair
https://repo.qst.go.jp/records/86417
https://repo.qst.go.jp/records/864172bd64f97-d5c9-4c23-9539-aac9cb069271
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-05-02 | |||||
| タイトル | ||||||
| タイトル | Theranostics of melanoma targeting metabotropic glutamate receptor 1 with a novel small-molecular radiopharmaceutical pair | |||||
| 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 |
Lin, Xie
× Lin, Xie× Masayuki, Hanyu× Masayuki, Fujinaga× Zhang, Lulu× Zhang, Yiding× Wakana, Mori× Kuan, Hu× Katsuyuki, Minegishi× Kotaro, Nagatsu× Kazunori, Kawamura× Zhang, Ming-Rong× Lin, Xie× Masayuki, Hanyu× Masayuki, Fujinaga× Zhang, Yiding× Wakana, Mori× Kuan, Hu× Katsuyuki, Minegishi× Kotaro, Nagatsu× Kazunori, Kawamura× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Metabotropic glutamate receptor 1 (GRM1) is aberrantly overexpressed in a wide variety of human solid tumors, such as melanoma，but not in normal peripheral organs (1). Therefore, GRM1 can be a widely–applicable target for the theranostics in oncology. Here, a novel small-molecular radiopharmaceutical pair, 3-iodo- N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-[11C]methylbenzamide ([11C]1) and 3-211At-astato-N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([211At]1), was designed and developed to target the GRM1 for the theranostics in melanomas (Fig.1). Method: [ 11C]1 was synthesized by reacting a N-desmethyl precursor with [11C]CH3OTf in the presence of NaOH at room temperature for 5 min. Radiolabeling of [211At]1 was performed by reaction of aryl tin precursor with NCS-containing 211At/MeOH solution. The theranostic potentials of the radiopharmaceutical pair were explored for PET imaging and radiotherapy in GRM1-positive B16F10 melanoma-bearing mice. Results: [ 11C]1 and [211At]1 were obtained with a radiochemical purity of greater than 99% and radiochemical yields of 19 ± 8 % and 46 ± 3%, respectively, based on the total radioactivity of used radionuclides. In vivo PET imaging of [ 11C]1 clearly visualized the targeted melanomas with a good tumor-to-background contrast (Fig. 1A). Ex vivo biodistribution study verified the persistent increase of [ 11C]1, which reached 12.29 ± 2.44 %ID/g tissue at 90 min in the targeted melanomas, and rapidly cleared from nontarget organs after intravenous injection. In the therapeutic studies, [211At]1 exhibited unequivocal and durable antitumor efficacy with only a single treatment (2.96 MBq) in the melanoma model, compared to the controls (0.38 ± 0.02 cm3 vs. 7.88 ± 1.28 cm3 at 13 days post-therapy) (Fig. 1B). No decrease in body weight, and no liver and kidney damage were observed through the examination period in melanoma mice injected with 2.96 MBq of [211At]1. Conclusion: The novel small-molecular radiopharmaceutical pair successfully visualized the GRM1-positive melanomas by [ 11C]1 with high contrast PET images, and further treated by [211At]1 without significant toxicity. The results highlight the good potential of using [ 11C]1 and [211At]1 as theranostic agents for the management of GRM1-positive tumors and should be further investigated in the theranostic field of oncology in the clinic. |
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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 | SNMMI2022 | |||||
| 発表年月日 | ||||||
| 日付 | 2022-06-14 | |||||
| 日付タイプ | Issued | |||||
