Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression
Abstract Background Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotempo...
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BMC
2025-01-01
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| Series: | Cancer Imaging |
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| Online Access: | https://doi.org/10.1186/s40644-025-00826-8 |
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| author | Lingzhou Zhao Jiali Gong Sisi Liao Wenhua Huang Jinhua Zhao Yan Xing |
| author_facet | Lingzhou Zhao Jiali Gong Sisi Liao Wenhua Huang Jinhua Zhao Yan Xing |
| author_sort | Lingzhou Zhao |
| collection | DOAJ |
| description | Abstract Background Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a 68Ga-labeled anti-PD-L1 nanobody, 68Ga-NODAGA-NM-01, for PET imaging of PD-L1. Methods Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with 68Ga without further purification under mild conditions. Results 68Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of 68Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, 68Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection. Conclusions 68Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort. Trial registration NCT02978196. Registered February 15, 2018. |
| format | Article |
| id | doaj-art-639584d00e8544e2848c6ea65976baf6 |
| institution | Kabale University |
| issn | 1470-7330 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Imaging |
| spelling | doaj-art-639584d00e8544e2848c6ea65976baf62025-02-02T12:40:48ZengBMCCancer Imaging1470-73302025-01-0125111010.1186/s40644-025-00826-8Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expressionLingzhou Zhao0Jiali Gong1Sisi Liao2Wenhua Huang3Jinhua Zhao4Yan Xing5Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou DistrictDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou DistrictDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou DistrictNanomab Technology LimitedDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou DistrictDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou DistrictAbstract Background Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a 68Ga-labeled anti-PD-L1 nanobody, 68Ga-NODAGA-NM-01, for PET imaging of PD-L1. Methods Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with 68Ga without further purification under mild conditions. Results 68Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of 68Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, 68Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection. Conclusions 68Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort. Trial registration NCT02978196. Registered February 15, 2018.https://doi.org/10.1186/s40644-025-00826-8NanobodyProgrammed death ligand-1Non-small-cell lung cancerPET imaging |
| spellingShingle | Lingzhou Zhao Jiali Gong Sisi Liao Wenhua Huang Jinhua Zhao Yan Xing Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression Cancer Imaging Nanobody Programmed death ligand-1 Non-small-cell lung cancer PET imaging |
| title | Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression |
| title_full | Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression |
| title_fullStr | Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression |
| title_full_unstemmed | Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression |
| title_short | Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression |
| title_sort | preclinical evaluation and preliminary clinical study of 68ga nodaga nm 01 for pet imaging of pd l1 expression |
| topic | Nanobody Programmed death ligand-1 Non-small-cell lung cancer PET imaging |
| url | https://doi.org/10.1186/s40644-025-00826-8 |
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