Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI
Abstract Glioblastoma is the most common and aggressive tumor of the central nervous system. Locoregional administration of therapeutic radiopharmaceuticals appears to be a promising modality for recurrent glioblastomas. In this study, fibroblast activation protein alpha (FAPα) targeting molecule fi...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03356-2 |
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| author | Huan Ma Tianzhen Ye Guofeng Qu Yilin Qin Jiali Liao Yuanyou Yang Wei Zhang Ning Liu Feize Li |
| author_facet | Huan Ma Tianzhen Ye Guofeng Qu Yilin Qin Jiali Liao Yuanyou Yang Wei Zhang Ning Liu Feize Li |
| author_sort | Huan Ma |
| collection | DOAJ |
| description | Abstract Glioblastoma is the most common and aggressive tumor of the central nervous system. Locoregional administration of therapeutic radiopharmaceuticals appears to be a promising modality for recurrent glioblastomas. In this study, fibroblast activation protein alpha (FAPα) targeting molecule fibroblast activation protein inhibitor-04 (FAPI-04) was conjugated to polydopamine (PDA) nanoparticles, and then, α-emitter astatine-211 was labeled onto the nanocomposite to form [211At]At-PDA-FAPI. In vitro, [211At]At-PDA-FAPI was able to significantly reduce the cell viability, induce DSB formation, arrest cell cycle at G2/M phase and promote cell apoptosis. Furthermore, [211At]At-PDA-FAPI exhibited effective tumor inhibition ability in U87MG xenografts. Mice received 0.56 MBq [211At]At-PDA-FAPI showed a reduced tumor volume of approximately 65% on the 9th day after injection, and the median survival in this group (48 days) was obviously improved compared with that in the saline group (18 days). Meanwhile, increased apoptosis was also observed in tumor sites after [211At]At-PDA-FAPI treatment. In addition, H&E analysis of major organs confirmed the biological safety of [211At]At-PDA-FAPI. This study provides an effective and promising strategy for locoregional treatment of glioblastoma. |
| format | Article |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-a5a4fae4c9c24cf69bf3c2f7537726b02025-08-20T03:16:46ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-03356-2Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPIHuan Ma0Tianzhen Ye1Guofeng Qu2Yilin Qin3Jiali Liao4Yuanyou Yang5Wei Zhang6Ning Liu7Feize Li8Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityDepartment of Nuclear Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityKey Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan UniversityAbstract Glioblastoma is the most common and aggressive tumor of the central nervous system. Locoregional administration of therapeutic radiopharmaceuticals appears to be a promising modality for recurrent glioblastomas. In this study, fibroblast activation protein alpha (FAPα) targeting molecule fibroblast activation protein inhibitor-04 (FAPI-04) was conjugated to polydopamine (PDA) nanoparticles, and then, α-emitter astatine-211 was labeled onto the nanocomposite to form [211At]At-PDA-FAPI. In vitro, [211At]At-PDA-FAPI was able to significantly reduce the cell viability, induce DSB formation, arrest cell cycle at G2/M phase and promote cell apoptosis. Furthermore, [211At]At-PDA-FAPI exhibited effective tumor inhibition ability in U87MG xenografts. Mice received 0.56 MBq [211At]At-PDA-FAPI showed a reduced tumor volume of approximately 65% on the 9th day after injection, and the median survival in this group (48 days) was obviously improved compared with that in the saline group (18 days). Meanwhile, increased apoptosis was also observed in tumor sites after [211At]At-PDA-FAPI treatment. In addition, H&E analysis of major organs confirmed the biological safety of [211At]At-PDA-FAPI. This study provides an effective and promising strategy for locoregional treatment of glioblastoma.https://doi.org/10.1038/s41598-025-03356-2Astatine-211Targeted alpha therapyFibroblast activation protein inhibitorGlioblastomaPolydopamine |
| spellingShingle | Huan Ma Tianzhen Ye Guofeng Qu Yilin Qin Jiali Liao Yuanyou Yang Wei Zhang Ning Liu Feize Li Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI Scientific Reports Astatine-211 Targeted alpha therapy Fibroblast activation protein inhibitor Glioblastoma Polydopamine |
| title | Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI |
| title_full | Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI |
| title_fullStr | Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI |
| title_full_unstemmed | Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI |
| title_short | Locoregional radionuclide therapy of glioblastoma with [211At]At-PDA-FAPI |
| title_sort | locoregional radionuclide therapy of glioblastoma with 211at at pda fapi |
| topic | Astatine-211 Targeted alpha therapy Fibroblast activation protein inhibitor Glioblastoma Polydopamine |
| url | https://doi.org/10.1038/s41598-025-03356-2 |
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