A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy
Boronophenylalanine (BPA) is the dominant boron delivery agent for boron neutron capture therapy (BNCT), and [18F]FBPA has been developed to assist the treatment planning for BPA-BNCT. However, the clinical application of BNCT has been limited by its inadequate tumor specificity due to the metabolic instability. In addition, the distinctive molecular structures between [18F]FBPA and BPA can be of concern as [18F]FBPA cannot quantitate boron concentration of BPA in a real-time manner. In this study, a metabolically stable boron-derived tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a theranostic agent for both boron delivery and cancer diagnosis, leading to PET imaging-guided BNCT of cancer. [18F]FBY was synthesized in high radiochemical yield (50%) and high radiochemical purity (98%). FBY showed high similarity with natural tyrosine. As shown in in vitro assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type amino acid transporter (LAT-1) dependent and reached up to 128 μg/106 cells. FBY displayed high stability in PBS solution. [18F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood = 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration of [18F]FBY tracer along with a therapeutic dose of FBY showed high accumulation in B16-F10 tumor and low normal tissue uptake. Correlation between PET-image and boron biodistribution was established, indicating the possibility of estimating boron concentration via a noninvasive approach. At last, with thermal neutron irradiation, B16-F10 tumor-bearing mice injected with FBY showed significantly prolonged median survival without exhibiting obvious systemic toxicity. In conclusion, FBY holds great potential as an efficient theranostic agent for imaging-guided BNCT by offering a possible solution of measuring local boron concentration through PET imaging.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Bioconjugate chemistry - 30(2019), 11 vom: 20. Nov., Seite 2870-2878 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Jiyuan [VerfasserIn] |
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| Links: |
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| Themen: |
42HK56048U |
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| Anmerkungen: |
Date Completed 22.09.2020 Date Revised 22.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.bioconjchem.9b00578 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM302004629 |
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| 100 | 1 | |a Li, Jiyuan |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 22.09.2020 | ||
| 500 | |a Date Revised 22.09.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Boronophenylalanine (BPA) is the dominant boron delivery agent for boron neutron capture therapy (BNCT), and [18F]FBPA has been developed to assist the treatment planning for BPA-BNCT. However, the clinical application of BNCT has been limited by its inadequate tumor specificity due to the metabolic instability. In addition, the distinctive molecular structures between [18F]FBPA and BPA can be of concern as [18F]FBPA cannot quantitate boron concentration of BPA in a real-time manner. In this study, a metabolically stable boron-derived tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a theranostic agent for both boron delivery and cancer diagnosis, leading to PET imaging-guided BNCT of cancer. [18F]FBY was synthesized in high radiochemical yield (50%) and high radiochemical purity (98%). FBY showed high similarity with natural tyrosine. As shown in in vitro assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type amino acid transporter (LAT-1) dependent and reached up to 128 μg/106 cells. FBY displayed high stability in PBS solution. [18F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood = 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration of [18F]FBY tracer along with a therapeutic dose of FBY showed high accumulation in B16-F10 tumor and low normal tissue uptake. Correlation between PET-image and boron biodistribution was established, indicating the possibility of estimating boron concentration via a noninvasive approach. At last, with thermal neutron irradiation, B16-F10 tumor-bearing mice injected with FBY showed significantly prolonged median survival without exhibiting obvious systemic toxicity. In conclusion, FBY holds great potential as an efficient theranostic agent for imaging-guided BNCT by offering a possible solution of measuring local boron concentration through PET imaging | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Radiopharmaceuticals |2 NLM | |
| 650 | 7 | |a Tyrosine |2 NLM | |
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| 700 | 1 | |a Shi, Yaxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zizhu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Lang, Lixin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaoyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhibo |e verfasserin |4 aut | |
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