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Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression
Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively relat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968138/ https://www.ncbi.nlm.nih.gov/pubmed/37259361 http://dx.doi.org/10.3390/ph16020213 |
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author | Xu, Liang Zhang, Lixia Liang, Beibei Zhu, Shiyu Lv, Gaochao Qiu, Ling Lin, Jianguo |
author_facet | Xu, Liang Zhang, Lixia Liang, Beibei Zhu, Shiyu Lv, Gaochao Qiu, Ling Lin, Jianguo |
author_sort | Xu, Liang |
collection | PubMed |
description | Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [(18)F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [(18)F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/μmol. [(18)F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [(18)F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [(18)F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [(18)F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors. |
format | Online Article Text |
id | pubmed-9968138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99681382023-02-27 Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression Xu, Liang Zhang, Lixia Liang, Beibei Zhu, Shiyu Lv, Gaochao Qiu, Ling Lin, Jianguo Pharmaceuticals (Basel) Article Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [(18)F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [(18)F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/μmol. [(18)F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [(18)F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [(18)F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [(18)F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors. MDPI 2023-01-30 /pmc/articles/PMC9968138/ /pubmed/37259361 http://dx.doi.org/10.3390/ph16020213 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xu, Liang Zhang, Lixia Liang, Beibei Zhu, Shiyu Lv, Gaochao Qiu, Ling Lin, Jianguo Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title | Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title_full | Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title_fullStr | Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title_full_unstemmed | Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title_short | Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression |
title_sort | design, synthesis, and biological evaluation of a small-molecule pet agent for imaging pd-l1 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968138/ https://www.ncbi.nlm.nih.gov/pubmed/37259361 http://dx.doi.org/10.3390/ph16020213 |
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