Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging
The blood–brain barrier (BBB) is likely to be intact during the early stages of brain metastatic melanoma development, and thereby inhibits sufficient drug delivery into the metastatic lesions. Our laboratory has been developing a system for boron drug delivery to brain cells via cerebrospinal fluid...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/2075-1729/12/11/1786 |
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| author | Sachie Kusaka Yumi Miyake Yugo Tokumaru Yuri Morizane Shingo Tamaki Yoko Akiyama Fuminobu Sato Isao Murata |
| author_facet | Sachie Kusaka Yumi Miyake Yugo Tokumaru Yuri Morizane Shingo Tamaki Yoko Akiyama Fuminobu Sato Isao Murata |
| author_sort | Sachie Kusaka |
| collection | DOAJ |
| description | The blood–brain barrier (BBB) is likely to be intact during the early stages of brain metastatic melanoma development, and thereby inhibits sufficient drug delivery into the metastatic lesions. Our laboratory has been developing a system for boron drug delivery to brain cells via cerebrospinal fluid (CSF) as a viable pathway to circumvent the BBB in boron neutron capture therapy (BNCT). BNCT is a cell-selective cancer treatment based on the use of boron-containing drugs and neutron irradiation. Selective tumor targeting by boron with minimal normal tissue toxicity is required for effective BNCT. Boronophenylalanine (BPA) is widely used as a boron drug for BNCT. In our previous study, we demonstrated that application of the CSF administration method results in high BPA accumulation in the brain tumor even with a low dose of BPA. In this study, we evaluate BPA biodistribution in the brain following application of the CSF method in brain-tumor-model rats (melanoma) utilizing matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). We observed increased BPA penetration to the tumor tissue, where the color contrast on mass images indicates the border of BPA accumulation between tumor and normal cells. Our approach could be useful as drug delivery to different types of brain tumor, including brain metastases of melanoma. |
| first_indexed | 2024-03-09T18:54:45Z |
| format | Article |
| id | doaj.art-603a79de3c1e46b3977355089d1f59a1 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T18:54:45Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-603a79de3c1e46b3977355089d1f59a12023-11-24T05:30:55ZengMDPI AGLife2075-17292022-11-011211178610.3390/life12111786Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry ImagingSachie Kusaka0Yumi Miyake1Yugo Tokumaru2Yuri Morizane3Shingo Tamaki4Yoko Akiyama5Fuminobu Sato6Isao Murata7Division of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanForefront Research Center, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka 560-0043, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanDivision of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Osaka, JapanThe blood–brain barrier (BBB) is likely to be intact during the early stages of brain metastatic melanoma development, and thereby inhibits sufficient drug delivery into the metastatic lesions. Our laboratory has been developing a system for boron drug delivery to brain cells via cerebrospinal fluid (CSF) as a viable pathway to circumvent the BBB in boron neutron capture therapy (BNCT). BNCT is a cell-selective cancer treatment based on the use of boron-containing drugs and neutron irradiation. Selective tumor targeting by boron with minimal normal tissue toxicity is required for effective BNCT. Boronophenylalanine (BPA) is widely used as a boron drug for BNCT. In our previous study, we demonstrated that application of the CSF administration method results in high BPA accumulation in the brain tumor even with a low dose of BPA. In this study, we evaluate BPA biodistribution in the brain following application of the CSF method in brain-tumor-model rats (melanoma) utilizing matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). We observed increased BPA penetration to the tumor tissue, where the color contrast on mass images indicates the border of BPA accumulation between tumor and normal cells. Our approach could be useful as drug delivery to different types of brain tumor, including brain metastases of melanoma.https://www.mdpi.com/2075-1729/12/11/1786boron neutron capture therapy (BNCT)cerebrospinal fluid (CSF) circulationbrain tumormelanoma model ratex vivo imagingmatrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) |
| spellingShingle | Sachie Kusaka Yumi Miyake Yugo Tokumaru Yuri Morizane Shingo Tamaki Yoko Akiyama Fuminobu Sato Isao Murata Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging Life boron neutron capture therapy (BNCT) cerebrospinal fluid (CSF) circulation brain tumor melanoma model rat ex vivo imaging matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) |
| title | Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging |
| title_full | Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging |
| title_fullStr | Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging |
| title_full_unstemmed | Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging |
| title_short | Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation in BNCT of Brain-Tumor-Model Rats—Ex Vivo Imaging of BPA Using MALDI Mass Spectrometry Imaging |
| title_sort | boron delivery to brain cells via cerebrospinal fluid csf circulation in bnct of brain tumor model rats ex vivo imaging of bpa using maldi mass spectrometry imaging |
| topic | boron neutron capture therapy (BNCT) cerebrospinal fluid (CSF) circulation brain tumor melanoma model rat ex vivo imaging matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) |
| url | https://www.mdpi.com/2075-1729/12/11/1786 |
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