Gaochao Lv, Nan Zhang, Junyi Zhu, Xin Hu, Qianhui Wang, Bingqing Qiu, Qingzhu Liu, Ling Qiu, Jianguo Lin
{"title":"基于小分子放射示踪剂的PD-L1表达和动力学PET成像的合成和临床前评估","authors":"Gaochao Lv, Nan Zhang, Junyi Zhu, Xin Hu, Qianhui Wang, Bingqing Qiu, Qingzhu Liu, Ling Qiu, Jianguo Lin","doi":"10.1007/s00259-025-07290-3","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Small molecule-based radiotracers offer several potential advantages in positron emission tomography (PET) imaging, and are therefore a promising approach for non-invasively and accurately monitoring of programmed death ligand 1 (PD-L1) expression in vivo. In this study, two small-molecule radiotracers were developed to assess PD-L1 expression and dynamics during treatments.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>[<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 were designed based on a phenoxymethyl-biphenyl scaffold with a tris-(hydroxymethyl)-aminomethane terminal group. The radiolabeling was achieved by a two-step method through the “click” chemistry. Cellular uptake assays in different tumor cells were performed to determine the specificity of the two tracers to PD-L1. The ability of [<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 to detect PD-L1 expression in vivo as well as to monitor PD-L1 dynamics during chemotherapy and immunotherapy was investigated <i>via</i> PET imaging.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The radiolabeling of [<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 was achieved with overall radiochemical yield of 15 ± 3% for [<sup>18</sup>F]LG-2 and 18 ± 5% for [<sup>18</sup>F]LG-3. In vitro cell uptake studies in tumor cells with varying PD-L1 levels demonstrated the specific binding of these tracers to PD-L1. PET imaging in mice bearing B16-F10 tumors displayed comparable tumor uptake of 6.45 ± 0.38%ID/mL for [<sup>18</sup>F]LG-2 and 5.64 ± 0.02%ID/mL for [<sup>18</sup>F]LG-3, while [<sup>18</sup>F]LG-3 showed nearly a 50% reduction in uptake in the liver and intestines compared to [<sup>18</sup>F]LG-2. PET signals of [<sup>18</sup>F]LG-3 in A375-hPD-L1, A375-hPD-L1/A375 and A375 tumor-bearing mice demonstrated a strong and linear correlation with PD-L1 expression levels. The dynamic of PD-L1 status in tumors after cisplatin and PD-L1 inhibitor treatments were accurately evaluated with [<sup>18</sup>F]LG-3 PET imaging.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The small-molecule radiotracer [<sup>18</sup>F]LG-3 is a promising candidate for evaluating PD-L1 expression and monitoring the dynamic of PD-L1 status during the treatment process.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"71 1","pages":""},"PeriodicalIF":8.6000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and preclinical evaluation of small molecule-based radiotracers for PET imaging of PD-L1 expression and dynamics\",\"authors\":\"Gaochao Lv, Nan Zhang, Junyi Zhu, Xin Hu, Qianhui Wang, Bingqing Qiu, Qingzhu Liu, Ling Qiu, Jianguo Lin\",\"doi\":\"10.1007/s00259-025-07290-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>Small molecule-based radiotracers offer several potential advantages in positron emission tomography (PET) imaging, and are therefore a promising approach for non-invasively and accurately monitoring of programmed death ligand 1 (PD-L1) expression in vivo. In this study, two small-molecule radiotracers were developed to assess PD-L1 expression and dynamics during treatments.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>[<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 were designed based on a phenoxymethyl-biphenyl scaffold with a tris-(hydroxymethyl)-aminomethane terminal group. The radiolabeling was achieved by a two-step method through the “click” chemistry. Cellular uptake assays in different tumor cells were performed to determine the specificity of the two tracers to PD-L1. The ability of [<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 to detect PD-L1 expression in vivo as well as to monitor PD-L1 dynamics during chemotherapy and immunotherapy was investigated <i>via</i> PET imaging.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>The radiolabeling of [<sup>18</sup>F]LG-2 and [<sup>18</sup>F]LG-3 was achieved with overall radiochemical yield of 15 ± 3% for [<sup>18</sup>F]LG-2 and 18 ± 5% for [<sup>18</sup>F]LG-3. In vitro cell uptake studies in tumor cells with varying PD-L1 levels demonstrated the specific binding of these tracers to PD-L1. PET imaging in mice bearing B16-F10 tumors displayed comparable tumor uptake of 6.45 ± 0.38%ID/mL for [<sup>18</sup>F]LG-2 and 5.64 ± 0.02%ID/mL for [<sup>18</sup>F]LG-3, while [<sup>18</sup>F]LG-3 showed nearly a 50% reduction in uptake in the liver and intestines compared to [<sup>18</sup>F]LG-2. PET signals of [<sup>18</sup>F]LG-3 in A375-hPD-L1, A375-hPD-L1/A375 and A375 tumor-bearing mice demonstrated a strong and linear correlation with PD-L1 expression levels. The dynamic of PD-L1 status in tumors after cisplatin and PD-L1 inhibitor treatments were accurately evaluated with [<sup>18</sup>F]LG-3 PET imaging.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>The small-molecule radiotracer [<sup>18</sup>F]LG-3 is a promising candidate for evaluating PD-L1 expression and monitoring the dynamic of PD-L1 status during the treatment process.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":\"71 1\",\"pages\":\"\"},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2025-04-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-025-07290-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-025-07290-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Synthesis and preclinical evaluation of small molecule-based radiotracers for PET imaging of PD-L1 expression and dynamics
Purpose
Small molecule-based radiotracers offer several potential advantages in positron emission tomography (PET) imaging, and are therefore a promising approach for non-invasively and accurately monitoring of programmed death ligand 1 (PD-L1) expression in vivo. In this study, two small-molecule radiotracers were developed to assess PD-L1 expression and dynamics during treatments.
Methods
[18F]LG-2 and [18F]LG-3 were designed based on a phenoxymethyl-biphenyl scaffold with a tris-(hydroxymethyl)-aminomethane terminal group. The radiolabeling was achieved by a two-step method through the “click” chemistry. Cellular uptake assays in different tumor cells were performed to determine the specificity of the two tracers to PD-L1. The ability of [18F]LG-2 and [18F]LG-3 to detect PD-L1 expression in vivo as well as to monitor PD-L1 dynamics during chemotherapy and immunotherapy was investigated via PET imaging.
Results
The radiolabeling of [18F]LG-2 and [18F]LG-3 was achieved with overall radiochemical yield of 15 ± 3% for [18F]LG-2 and 18 ± 5% for [18F]LG-3. In vitro cell uptake studies in tumor cells with varying PD-L1 levels demonstrated the specific binding of these tracers to PD-L1. PET imaging in mice bearing B16-F10 tumors displayed comparable tumor uptake of 6.45 ± 0.38%ID/mL for [18F]LG-2 and 5.64 ± 0.02%ID/mL for [18F]LG-3, while [18F]LG-3 showed nearly a 50% reduction in uptake in the liver and intestines compared to [18F]LG-2. PET signals of [18F]LG-3 in A375-hPD-L1, A375-hPD-L1/A375 and A375 tumor-bearing mice demonstrated a strong and linear correlation with PD-L1 expression levels. The dynamic of PD-L1 status in tumors after cisplatin and PD-L1 inhibitor treatments were accurately evaluated with [18F]LG-3 PET imaging.
Conclusion
The small-molecule radiotracer [18F]LG-3 is a promising candidate for evaluating PD-L1 expression and monitoring the dynamic of PD-L1 status during the treatment process.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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