A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy
Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranost...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02312-y |
| _version_ | 1797258986994532352 |
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| author | Hongzhang Yang Xinying Zeng Jia Liu Jingchao Li Yun Li Qinglin Zhang Linlin Shu Huanhuan Liu Xueqi Wang Yuanyuan Liang Ji Hu Lumei Huang Zhide Guo Xianzhong Zhang |
| author_facet | Hongzhang Yang Xinying Zeng Jia Liu Jingchao Li Yun Li Qinglin Zhang Linlin Shu Huanhuan Liu Xueqi Wang Yuanyuan Liang Ji Hu Lumei Huang Zhide Guo Xianzhong Zhang |
| author_sort | Hongzhang Yang |
| collection | DOAJ |
| description | Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstract |
| first_indexed | 2024-04-24T23:02:15Z |
| format | Article |
| id | doaj.art-171d20221cc74601af029e0e77dc904e |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-24T23:02:15Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-171d20221cc74601af029e0e77dc904e2024-03-17T12:37:15ZengBMCJournal of Nanobiotechnology1477-31552024-03-0122111210.1186/s12951-024-02312-yA proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategyHongzhang Yang0Xinying Zeng1Jia Liu2Jingchao Li3Yun Li4Qinglin Zhang5Linlin Shu6Huanhuan Liu7Xueqi Wang8Yuanyuan Liang9Ji Hu10Lumei Huang11Zhide Guo12Xianzhong Zhang13State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityPET Center, Department of Nuclear Medicine, School of Medicine, The First Affiliated Hospital, Zhejiang UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityHTA Co., Ltd.State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityTheranostics and Translational Research Center, Institute of Clinical Medicine & Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02312-yRadiotheranosticsClick-mediated bioorthogonal chemistryTumor signal amplificationPretargetingPSMA |
| spellingShingle | Hongzhang Yang Xinying Zeng Jia Liu Jingchao Li Yun Li Qinglin Zhang Linlin Shu Huanhuan Liu Xueqi Wang Yuanyuan Liang Ji Hu Lumei Huang Zhide Guo Xianzhong Zhang A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy Journal of Nanobiotechnology Radiotheranostics Click-mediated bioorthogonal chemistry Tumor signal amplification Pretargeting PSMA |
| title | A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy |
| title_full | A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy |
| title_fullStr | A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy |
| title_full_unstemmed | A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy |
| title_short | A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy |
| title_sort | proof of concept study on bioorthogonal based pretargeting and signal amplify radiotheranostic strategy |
| topic | Radiotheranostics Click-mediated bioorthogonal chemistry Tumor signal amplification Pretargeting PSMA |
| url | https://doi.org/10.1186/s12951-024-02312-y |
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