Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages
Boron neutron capture therapy (BNCT) is a binary therapeutic technique employing a boron agent to be delivered to the tumor site followed by the irradiation of neutrons. Biofunctional molecules/nanoparticles labeled with F-18 can provide an initial pharmacokinetic profile of patients to guide the su...
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/1/93 |
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| author | Jin-Pei Deng Chung-Shan Yu |
| author_facet | Jin-Pei Deng Chung-Shan Yu |
| author_sort | Jin-Pei Deng |
| collection | DOAJ |
| description | Boron neutron capture therapy (BNCT) is a binary therapeutic technique employing a boron agent to be delivered to the tumor site followed by the irradiation of neutrons. Biofunctional molecules/nanoparticles labeled with F-18 can provide an initial pharmacokinetic profile of patients to guide the subsequent treatment planning procedure of BNCT. Borono phenylalanine (BPA), recognized by the <i><span style="font-variant: small-caps;">l</span></i>-type amino acid transporter, can cross the blood-brain barrier and be accumulated in gliomas. The radiofluoro BNCT agents are reviewed by considering (1) less cytotoxicity, (2) diagnosing and therapeutic purposes, (3) aqueous solubility and extraction route, as well as (4), the trifluoroborate effect. A trifluoroborate-containing amino acid such as fluoroboronotyrosine (FBY) represents an example with both functionalities of imaging and therapeutics. Comparing with the insignificant cytotoxicity of clinical BPA with IC<sub>50</sub> > 500 μM, FBY also shows minute toxicity with IC<sub>50</sub> > 500 μM. [<sup>18</sup>F]FBY is a potential diagnostic agent for its tumor to normal accumulation (T/N) ratio, which ranges from 2.3 to 24.5 from positron emission tomography, whereas the T/N ratio of FBPA is greater than 2.5. Additionally, in serving as a BNCT therapeutic agent, the boron concentration of FBY accumulated in gliomas remains uncertain. The solubility of 3-BPA is better than that of BPA, as evidenced by the cerebral dose of 3.4%ID/g vs. 2.2%ID/g, respectively. While the extraction route of <i><span style="font-variant: small-caps;">d</span></i>-BPA differs from that of BPA, an impressive T/N ratio of 6.9 vs. 1.5 is noted. [<sup>18</sup>F]FBPA, the most common clinical boron agent, facilitates the application of BPA in clinical BNCT. In addition to [<sup>18</sup>F]FBY, [<sup>18</sup>F] trifluoroborated nucleoside analog obtained through 1,3-dipolar cycloaddition shows marked tumoral uptake of 1.5%ID/g. Other examples using electrophilic and nucleophilic fluorination on the boron compounds are also reviewed, including diboronopinacolone phenylalanine and nonsteroidal anti-inflammatory agents. |
| first_indexed | 2024-03-09T11:29:48Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
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| spelling | doaj.art-b50afe3a5e9f418296fcb2defdc76baf2023-11-30T23:55:42ZengMDPI AGPharmaceuticals1424-82472023-01-011619310.3390/ph16010093Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F LinkagesJin-Pei Deng0Chung-Shan Yu1Department of Chemistry, Tamkang University, Tamsui, New Taipei City 251301, TaiwanDepartment of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu 30013, TaiwanBoron neutron capture therapy (BNCT) is a binary therapeutic technique employing a boron agent to be delivered to the tumor site followed by the irradiation of neutrons. Biofunctional molecules/nanoparticles labeled with F-18 can provide an initial pharmacokinetic profile of patients to guide the subsequent treatment planning procedure of BNCT. Borono phenylalanine (BPA), recognized by the <i><span style="font-variant: small-caps;">l</span></i>-type amino acid transporter, can cross the blood-brain barrier and be accumulated in gliomas. The radiofluoro BNCT agents are reviewed by considering (1) less cytotoxicity, (2) diagnosing and therapeutic purposes, (3) aqueous solubility and extraction route, as well as (4), the trifluoroborate effect. A trifluoroborate-containing amino acid such as fluoroboronotyrosine (FBY) represents an example with both functionalities of imaging and therapeutics. Comparing with the insignificant cytotoxicity of clinical BPA with IC<sub>50</sub> > 500 μM, FBY also shows minute toxicity with IC<sub>50</sub> > 500 μM. [<sup>18</sup>F]FBY is a potential diagnostic agent for its tumor to normal accumulation (T/N) ratio, which ranges from 2.3 to 24.5 from positron emission tomography, whereas the T/N ratio of FBPA is greater than 2.5. Additionally, in serving as a BNCT therapeutic agent, the boron concentration of FBY accumulated in gliomas remains uncertain. The solubility of 3-BPA is better than that of BPA, as evidenced by the cerebral dose of 3.4%ID/g vs. 2.2%ID/g, respectively. While the extraction route of <i><span style="font-variant: small-caps;">d</span></i>-BPA differs from that of BPA, an impressive T/N ratio of 6.9 vs. 1.5 is noted. [<sup>18</sup>F]FBPA, the most common clinical boron agent, facilitates the application of BPA in clinical BNCT. In addition to [<sup>18</sup>F]FBY, [<sup>18</sup>F] trifluoroborated nucleoside analog obtained through 1,3-dipolar cycloaddition shows marked tumoral uptake of 1.5%ID/g. Other examples using electrophilic and nucleophilic fluorination on the boron compounds are also reviewed, including diboronopinacolone phenylalanine and nonsteroidal anti-inflammatory agents.https://www.mdpi.com/1424-8247/16/1/93BNCTbrain tumortyrosineboronophenyl alanineBPAFBPA |
| spellingShingle | Jin-Pei Deng Chung-Shan Yu Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages Pharmaceuticals BNCT brain tumor tyrosine boronophenyl alanine BPA FBPA |
| title | Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages |
| title_full | Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages |
| title_fullStr | Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages |
| title_full_unstemmed | Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages |
| title_short | Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of <sup>18</sup>F-Labeled C-F and B-F Linkages |
| title_sort | recent development of radiofluorination of boron agents for boron neutron capture therapy of tumor creation of sup 18 sup f labeled c f and b f linkages |
| topic | BNCT brain tumor tyrosine boronophenyl alanine BPA FBPA |
| url | https://www.mdpi.com/1424-8247/16/1/93 |
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