Organotrifluoroborate enhances tumor targeting of fibroblast activation protein inhibitors for targeted radionuclide therapy
Purpose Fibroblast activation protein (FAP) is a pan-cancer target and now the state-of-the-art to develop radiopharmaceuticals. FAP inhibitors have been of great success in developing imaging tracers. Yet, the overly rapid clearance cannot match with the long half-lives of regular therapeutic radionuclides. Though strategies that aim to elongate the circulation of FAPIs are being developed, here we describe an innovation that uses α-emitters of short half-lives (e.g., 213Bi) to pair the rapid pharmacokinetics of FAPIs. Methods An organotrifluoroborate linker is engineered to FAPIs to give two advantages: (1) selectively increases tumor uptake and retention; (2) facile 18F-radiolabeling for positron emission tomography to guide radiotherapy with α-emitters, which can hardly be traced in general. Results The organotrifluoroborate linker helps to improve the internalization in cancer cells, resulting in notably higher tumor uptake while the background is clean. In FAP-expressed tumor-bearing mice, this FAPI labeled with 213Bi, a short half-life α-emitter, exhibits almost complete suppression to tumor growth while the side effect is negligible. Additional data shows that this strategy is generally applicable to guide other α-emitters, such as 212Bi, 212Pb, and 149Tb. Conclusion The organotrifluoroborate linker may be of importance to optimize FAP-targeted radiopharmaceuticals, and the short half-lived α-emitters may be of choice for the rapid-cleared small molecule-based radiopharmaceuticals..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
European journal of nuclear medicine & molecular imaging - 50(2023), 9 vom: 27. Apr., Seite 2636-2646 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yu [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Bismuth-213 |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s00259-023-06230-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC2144270821 |
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| 520 | |a Purpose Fibroblast activation protein (FAP) is a pan-cancer target and now the state-of-the-art to develop radiopharmaceuticals. FAP inhibitors have been of great success in developing imaging tracers. Yet, the overly rapid clearance cannot match with the long half-lives of regular therapeutic radionuclides. Though strategies that aim to elongate the circulation of FAPIs are being developed, here we describe an innovation that uses α-emitters of short half-lives (e.g., 213Bi) to pair the rapid pharmacokinetics of FAPIs. Methods An organotrifluoroborate linker is engineered to FAPIs to give two advantages: (1) selectively increases tumor uptake and retention; (2) facile 18F-radiolabeling for positron emission tomography to guide radiotherapy with α-emitters, which can hardly be traced in general. Results The organotrifluoroborate linker helps to improve the internalization in cancer cells, resulting in notably higher tumor uptake while the background is clean. In FAP-expressed tumor-bearing mice, this FAPI labeled with 213Bi, a short half-life α-emitter, exhibits almost complete suppression to tumor growth while the side effect is negligible. Additional data shows that this strategy is generally applicable to guide other α-emitters, such as 212Bi, 212Pb, and 149Tb. Conclusion The organotrifluoroborate linker may be of importance to optimize FAP-targeted radiopharmaceuticals, and the short half-lived α-emitters may be of choice for the rapid-cleared small molecule-based radiopharmaceuticals. | ||
| 650 | 4 | |a Positron emission tomography | |
| 650 | 4 | |a Targeted radionuclide therapy | |
| 650 | 4 | |a Bismuth-213 | |
| 650 | 4 | |a Fibroblast activation protein | |
| 650 | 4 | |a Organotrifluoroborate | |
| 700 | 1 | |a Tang, Haocheng |4 aut | |
| 700 | 1 | |a Song, Tianchi |4 aut | |
| 700 | 1 | |a Xu, Mengxin |4 aut | |
| 700 | 1 | |a Chen, Junyi |4 aut | |
| 700 | 1 | |a Cui, Xi-Yang |4 aut | |
| 700 | 1 | |a Han, Yuxiang |4 aut | |
| 700 | 1 | |a Li, Zhu |4 aut | |
| 700 | 1 | |a Liu, Zhibo |0 (orcid)0000-0002-5587-4165 |4 aut | |
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