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Develop a peptide-based PET radiotracer for imaging PD-L1 expression in cancer.
https://repo.qst.go.jp/records/76121
https://repo.qst.go.jp/records/761214157d456-a8eb-4f48-b843-df62938c714a
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-06-03 | |||||
| タイトル | ||||||
| タイトル | Develop a peptide-based PET radiotracer for imaging PD-L1 expression in cancer. | |||||
| 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 |
Kuan, Hu
× Kuan, Hu× Xie, Lin× Hanyu, Masayuki× Zhang, Yiding× Ming-Rong, Zhang× Kuan, Hu× Xie, Lin× Hanyu, Masayuki× Zhang, Yiding× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Immune checkpoint blockade has emerged as a promising cancer treatment paradigm. Unfortunately, there are still a large number of patients and malignancies that do not respond to this therapy. A major barrier to validating biomarkers for the prediction and monitoring of responders to clinical checkpoint blockade has been the lack of imaging tools to accurately assess dynamic immune checkpoint expression. The programmed cell death ligand 1 (PD-L1) is expressed in many cancers, and is an important contributor to the maintenance of immunosuppressive tumor microenvironment. PD-L1 is a prominent target for cancer immunotherapy [1, 2]. An Octapeptide (PWZ-1), was recently screened with high binding affinity for PD-L1 (KD ≈ 10 nM). Here we examine the feasibility of developing the octapeptide as a radiotracer for noninvasive detection of PD-L1 expression in tumors by PET. Methods: PWZ-1 peptide was conjugated with DOTA as a chelator for radioisotope labelling. The binding affinity of PWZ-1-NOTA was evaluated by surface plasmon resonance. PWZ-1 was subjected to radiolabeling with copper-64 and the radiolabeling conditions were optimized. The resulting [64Cu]PWZ-1 was assessed for stability in saline and in mouse serum. The in vitro specificity of the radiolabeled peptides for two PD-L1(+) cell lines MDA-MB-231 and B16F10 was tested. Next, we performed small animal PET imaging in tumor-bearing mice with the radiolabeled peptide which was injected via tail vein. The ex vivo biodistribution of [64Cu]PWZ-1 in mice was also conducted. Results: Surface plasmon resonance showed the DOTA-conjugated PWZ-1 with a similar binding affinity with PWZ-1. Synthesis of [64Cu]PWZ-1 provided radiochemical purity >99% after purification and formulation. Biodistribution in mice demonstrated 5-10 percentage of injected dose per gram (%ID/g) in MDAMB231and B16F10 tumors, respectively, at 1 h postinjection, with high binding specificity noted with coinjection of excess unlabelled PWZ-1. PET imaging showed high uptake contrast in all tumor models tested. Conclusion: We demonstrated the specificity of [64Cu]PWZ-1 to detect PD-L1 expression in multiple xenograft models with variable PD-L1 expressions and described its biodistribution and pharmacokinetics. In addition, the radiolabeling and purification conditions tested for preparation of [64Cu]PWZ-1 could be easily modified to facilitate a kit preparation of the radiotracer for PD-L1 imaging. Such 64Cu-labeled PD-L1 imaging agents with short biological half-life and fit within the routine clinical work flow enables therapy monitoring and stratification of patients in the field of immuno-oncology. References: [1] L. M. Roy, et al. Proc. Natl. Sci. USA. 2015, 112, E6506-14. [2] C. Truillet, et al. Bioconjugate. Chem. 2018, 29, 96-103. |
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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 | ISRS2019 | |||||
| 発表年月日 | ||||||
| 日付 | 2019-05-28 | |||||
| 日付タイプ | Issued | |||||
