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PET imaging of PD-L1 overexpressing tumors with a 68Ga labeled D-dodecapeptide
https://repo.qst.go.jp/records/82856
https://repo.qst.go.jp/records/8285645bc0648-3bff-4eb8-9d41-88687f27d464
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-05-06 | |||||
| タイトル | ||||||
| タイトル | PET imaging of PD-L1 overexpressing tumors with a 68Ga labeled D-dodecapeptide | |||||
| 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× Lin, Xie× Masayuki, Hanyu× Zhang, Yiding× Zhang, Ming-Rong× Kuan, Hu× Lin, Xie× Masayuki, Hanyu× Zhang, Yiding× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: D-peptides are hyper-resistant to proteolytic degradation in L-homochiral living subjects, making them remarkedly increased gut, blood plasma, and intracellular half-lives. D-peptides are theoretically ideal drug candidates, however, the potential of D-peptides in radiopharmaceuticals is rarely explored. Recently, a D-dodecapeptide antagonist (DPA) identified by mirror-image phage display revealed high efficacy to block the programmed death-ligand 1 (PD-L1)/programmed death 1 (PD-1) interaction in animal models. In this work, we report the radiolabeling of DPA with 68Ga and study its metabolism and target engagement in tumor-bearing mice using PET. Methods: The PD-L1 protein expression in the human glioblastoma U87MG cell line was analyzed by flow cytometry and immunofluorescence imaging. The stability of [68Ga]DPA in saline and mouse serum was examined by radio HPLC and TLC. The cellular uptake of [68Ga]DPA into U87MG cells was measured at 15, 30, 60, and 120 min after co-incubation. For PET imaging, we inoculated 1×106 U87MG cells to the left flank of Balb/c nude mice subcutaneously. When the tumors grow to ̴100 mm3 at 7 days after inoculation, mice were injected with [68Ga]DPA (0.5 mCi per mouse) intravenously. Dynamic PET was performed from 0-60 min postinjection. To comprehensively profile the in vivo distribution of the tracer, ex vivo distribution was carried out in Balb/c nude mice bearing U87MG tumors. Mice were sacrificed at 5, 30, 60, and 120 min postinjection of the tracer (0.05 mCi per mouse). The tumor and organs were harvested and subjected to gamma counter measurement. Based on the ex vivo biodistribution data, we calculated the tumor to blood, tumor to liver, and tumor to muscle ratios. As a PD-L1 negative control, we also performed PET imaging in Bon-1 tumor-bearing Balb/c nude mice. Finally, the PD-L1 expression level in U87MG and Bon-1 tumor tissue was immunohistologically stained and compared. Results: The U87G cells were detected with approximately 60% subpopulation that express PD-L1 protein. The uptake of the tracer by U87MG cells showed a time-dependent manner and increased from 2%AD at 15 min of co-incubation to 4%AD at 120 min of co-incubation. Whole-body PET imaging showed substantial [68Ga]DPA accumulation in U87MG tumors at 30 and 60 min postinjection. The highest radioactivity appeared in the kidney and bladder, and non-striking radioactivity was noticed in other tissues, such as the liver and lung. Ex vivo biodistribution data verified the observation in the PET study. The washout of the tracers from nonspecific organs such as blood, liver, and muscle was significantly faster than that in the tumor, indicating PD-L1 specific retention in the U87MG tumor. The optimum image contrast was achieved at 60 min postinjection. Immunohistological analysis revealed obvious PD-L1 expression in U87MG tumors but rare of that in Bon-1 tumors. Conclusions: We have successfully labeled the DPA with 68Ga. The in vivo profile of [68Ga]DPA suggested it a potential radiotracer for PD-L1 visualization. Our study paves the way for exploiting D-peptides as radiopharmaceuticals to manage cancer, both as PET tracers and radiotheranostics agents. Acknowledgement: We thank the financial support from the JSPS KAKENHI grant no. 19K17156. |
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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 | eSRS | |||||
| 発表年月日 | ||||||
| 日付 | 2021-05-17 | |||||
| 日付タイプ | Issued | |||||
