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Visualizing the dynamics of checkpoint protein IDO1 reveals host antitumor responses activated by a combination of immunotherapy and chemotherapy with 11C-L-1MTrp PET
https://repo.qst.go.jp/records/72759
https://repo.qst.go.jp/records/72759196e161c-77dc-47a2-b4ba-3affd8a8fadd
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-04-27 | |||||
| タイトル | ||||||
| タイトル | Visualizing the dynamics of checkpoint protein IDO1 reveals host antitumor responses activated by a combination of immunotherapy and chemotherapy with 11C-L-1MTrp PET | |||||
| 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 |
Xie, Lin
× Xie, Lin× Shimokawa, Takashi× Zhang, Yiding× Jiang, Cuiping× Wakizaka, Hidekatsu× Kumata, Katsushi× Nengaki, Nobuki× Zhang, Ming-Rong× 謝 琳× 下川 卓志× 張 一鼎× 脇坂 秀克× 熊田 勝志× 念垣 信樹× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background and Aims: Capturing host antitumor responses to combinatorial immunotherapy remains a major challenge. From the standpoint of immunology, cancer immunotherapy is considered as a “double edged sword” in that it can trigger two opposite immunologic processes to limit potential toxicity associated with excessive response [1]. So tracking its opposite immune regulatory-mechanisms has potential as surrogates for defining the complex scenarios. In this study, we developed a small-molecular positron emission tomography/computed tomography (PET/CT) method targeting the checkpoint protein, IDO1, in tumor-bearing hosts to address this challenge. \nMethods: Leveraging the very short-lived positron emitter carbon-11 (11C; half-life: 20.4 min) to label a small molecule IDO1 inhibitor, levorotary (L) form of 1-methyl-tryptophan (1MTrp), we developed a radioprobe 1-N-11C-methyl-L-tryptophan (11C-L-1MTrp) [2]. Using PET/CT with 11C-L-1MTrp, we specifically and serially monitored IDO1 changes to reveal the antitumor immune response in melanoma-bearing immunocompetent mice treated with immunotherapy combinatorial chemotherapy. Animal studies were approved by the Animal Ethics Committee of the National Institutes for Quantum and Radiological Science and Technology. \nResults: On combining the 11C-L-1MTrp and the imaging power of PET/CT, we observed that IDO1 exhibited dynamic alterations in mesenteric lymph nodes (MLN) and the caput of the epididymis, and observed a connection between active responses to combinatorial immunotherapy in immunocompetent mice. These imaging markers exhibited an empirical cut-off value of 7.023 %ID/g for radioactivity in MLN, which provided an early-on-treatment indicator with 97.92 % specificity. A cut-off value of 8.313 %ID/g in the epididymis offered a sensitivity of 100 % as an index of immune exhaustion. \nConclusion: 11C-L-1MTrp-PET/CT provided a visual method to capture the dynamics of host responses to combinatorial immunotherapies, with near-term clinical application. \nReferences: [1]. Pardoll DM. Nature Rev. Cancer. 2012, 12, 252. [2] Xie, L. et al. Sci. Rep.2015, 5,16417. |
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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 | 12th World Congress of the World Federation of Nuclear Medicine and Biology | |||||
| 発表年月日 | ||||||
| 日付 | 2018-04-23 | |||||
| 日付タイプ | Issued | |||||
