Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression
Immunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, on...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1487 |
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| author | Yong Huang Chengze Li Zhongjing Li Qiong Wang Size Huang Qi Liu Ying Liang |
| author_facet | Yong Huang Chengze Li Zhongjing Li Qiong Wang Size Huang Qi Liu Ying Liang |
| author_sort | Yong Huang |
| collection | DOAJ |
| description | Immunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, ongoing clinical studies utilize a few PD-L1 radiotracers to assess PD-L1 expression as a predictive biomarker for immunotherapy. Here, we present a novel positron emission tomography (PET) radiotracer called [<sup>68</sup>Ga]BMSH, which is derived from a small molecule inhibitor specifically targeting the binding site of PD-L1. The inhibitor was modified to optimize its in vivo pharmacokinetic properties and enable chelation of <sup>68</sup>Ga. In vitro evaluation revealed [<sup>68</sup>Ga]BMSH possessed a strong binding affinity, high specificity, and rapid internalization in PD-L1 overexpressing cells. Biodistribution studies showed that PD-L1 overexpressing tumors had an uptake of [<sup>68</sup>Ga]BMSH at 4.22 ± 0.65%ID/g in mice, while the number was 2.23 ± 0.41%ID/g in PD-L1 low-expressing tumors. Micro-PET/CT imaging of tumor-bearing mice further confirmed that, compared to [<sup>18</sup>F]FDG, [<sup>68</sup>Ga]BMSH can specifically identify tumors with varying levels of PD-L1 expression. Our findings suggest that the [<sup>68</sup>Ga]BMSH is a PD-L1 radioligand with ideal imaging properties, and its further application in the clinical screening of PD-L1 overexpressing tumors may improve ORR for immunotherapy. |
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| language | English |
| last_indexed | 2024-03-10T20:58:58Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-b2bfecd1e3754530a460a0709e5922b32023-11-19T17:43:13ZengMDPI AGPharmaceuticals1424-82472023-10-011610148710.3390/ph16101487Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 ExpressionYong Huang0Chengze Li1Zhongjing Li2Qiong Wang3Size Huang4Qi Liu5Ying Liang6Department of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaDepartment of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaDepartment of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaDepartment of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaDepartment of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaInternational Cancer Center, Shenzhen University School of Medicine, Shenzhen University, Shenzhen 518057, ChinaDepartment of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaImmunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, ongoing clinical studies utilize a few PD-L1 radiotracers to assess PD-L1 expression as a predictive biomarker for immunotherapy. Here, we present a novel positron emission tomography (PET) radiotracer called [<sup>68</sup>Ga]BMSH, which is derived from a small molecule inhibitor specifically targeting the binding site of PD-L1. The inhibitor was modified to optimize its in vivo pharmacokinetic properties and enable chelation of <sup>68</sup>Ga. In vitro evaluation revealed [<sup>68</sup>Ga]BMSH possessed a strong binding affinity, high specificity, and rapid internalization in PD-L1 overexpressing cells. Biodistribution studies showed that PD-L1 overexpressing tumors had an uptake of [<sup>68</sup>Ga]BMSH at 4.22 ± 0.65%ID/g in mice, while the number was 2.23 ± 0.41%ID/g in PD-L1 low-expressing tumors. Micro-PET/CT imaging of tumor-bearing mice further confirmed that, compared to [<sup>18</sup>F]FDG, [<sup>68</sup>Ga]BMSH can specifically identify tumors with varying levels of PD-L1 expression. Our findings suggest that the [<sup>68</sup>Ga]BMSH is a PD-L1 radioligand with ideal imaging properties, and its further application in the clinical screening of PD-L1 overexpressing tumors may improve ORR for immunotherapy.https://www.mdpi.com/1424-8247/16/10/1487[<sup>68</sup>Ga]BMSHimmunotherapyprogrammed death-ligand 1positron emission-computed tomography |
| spellingShingle | Yong Huang Chengze Li Zhongjing Li Qiong Wang Size Huang Qi Liu Ying Liang Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression Pharmaceuticals [<sup>68</sup>Ga]BMSH immunotherapy programmed death-ligand 1 positron emission-computed tomography |
| title | Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression |
| title_full | Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression |
| title_fullStr | Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression |
| title_full_unstemmed | Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression |
| title_short | Development and Preclinical Evaluation of [<sup>68</sup>Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression |
| title_sort | development and preclinical evaluation of sup 68 sup ga bmsh as a new potent positron emission tomography tracer for imaging programmed death ligand 1 expression |
| topic | [<sup>68</sup>Ga]BMSH immunotherapy programmed death-ligand 1 positron emission-computed tomography |
| url | https://www.mdpi.com/1424-8247/16/10/1487 |
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