Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Boron Carriers
2.2. Cell Culture
2.3. F98 Glioma-Bearing Rat Brain Tumor Model
2.4. In Vitro Cellular Uptake Experiments
2.5. In Vitro Neutron-Irradiation Experiments
2.6. Biodistribution of Boron in the F98 Glioma-Bearing Rats after Intravenous Administration of Each Boron Carrier
2.7. Survival Analysis of the In Vivo Neutron-Irradiation Experiments
2.8. Estimated Physical Dose and Biologically Photon-Equivalent Dose
2.9. Statistical Analysis
3. Results
3.1. In Vitro Cellular Boron Uptake Experiments in F98, C6 Glioma, and 9L Gliosarcoma Cells
3.2. Neutron Irradiation in the In Vitro Experiments
3.3. Biodistribution of Boron in the F98 Glioma-Bearing Rats after Intravenous Administration of Each Boron Carrier
3.4. Survival Analysis of the In Vivo Neutron-Irradiation Experiments
3.5. Estimation of Physical and Biologically Photon-Equivalent Doses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Boron Carrier a | Boron Concentration (µg B/109 Cells) ± SD b | |||||
---|---|---|---|---|---|---|
1 h | 6 h | 24 h | 24 + 1 h | 24 + 6 h | 24 + 24 h | |
BPA | 12.9 ± 1.4 | 15.8 ± 1.4 | 32.6 ± 0.6 | 4.8 ± 0.2 | 3.9 ± 1.1 | 3.1 ± 0.5 |
cRGD-MID-AC | 7.3 ± 0.6 | 8.1 ± 1.0 | 14.0 ± 0.1 | 10.5 ± 0.4 | 10.1 ± 0.2 | 4.8 ± 0.4 |
cRGD + MID | 4.3 ± 0.5 | 6.4 ± 0.7 | 5.1 ± 0.5 | 3.3 ± 0.3 | 2.9 ± 0.04 | 1.1 ± 0.1 |
Boron Carrier a | Boron Concentration (µg B/109 Cells) ± SD b | |||||
---|---|---|---|---|---|---|
1 h | 6 h | 24 h | 24 + 1 h | 24 + 6 h | 24 + 24 h | |
BPA | 11.2 ± 1.6 | 12.3 ± 2.1 | 14.7 ± 1.5 | 2.31 ± 0.1 | 2.29 ± 0.1 | 1.1 ± 0.1 |
cRGD-MID-AC | 6.3 ± 0.3 | 7.1 ± 0.5 | 8.4 ± 0.2 | 7.5 ± 1.1 | 7.0 ± 1.1 | 2.2 ± 0.1 |
cRGD + MID | 5.6 ± 0.6 | 6.0 ± 1.0 | 4.8 ± 0.3 | 3.7 ± 0.3 | 3.6 ± 0.2 | 1.1 ± 0.03 |
Boron Carrier a | Boron Concentration (µg B/109 Cells) ± SD b | |||||
---|---|---|---|---|---|---|
1 h | 6 h | 24 h | 24 + 1 h | 24 + 6 h | 24 + 24 h | |
BPA | 15.8 ± 1.3 | 41.3 ± 0.9 | 46.4 ± 0.2 | 10.8 ± 0.3 | 7.6 ± 0.7 | 5.9 ± 0.3 |
cRGD-MID-AC | 6.1 ± 0.5 | 9.4 ± 0.4 | 16.5 ± 1.6 | 14.2 ± 1.5 | 11.7 ± 0.9 | 5.2 ± 0.7 |
cRGD + MID | 6.0 ± 1.4 | 7.9 ± 0.1 | 7.8 ± 0.4 | 4.6 ± 0.2 | 4.2 ± 0.1 | 1.9 ± 0.2 |
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Boron Carrier a | Time b (h) | n c | Boron Concentration ± SD (µg B/g) d | Ratio | |||
---|---|---|---|---|---|---|---|
Tumor | Brain | Blood | T/Br e | T/Bl f | |||
cRGD-MID-AC | 2.5 | 4 | 10.1 ± 1.6 | 0.8 ± 0.2 | 41.6 ± 5.6 | 12.5 | 0.2 |
8 | 4 | 17.0 ± 1.8 | 0.9 ± 0.1 | 40.3 ± 8.4 | 18.5 | 0.4 | |
24 | 4 | 13.1 ± 1.9 | 0.7 ± 0.1 | 17.7 ± 2.3 | 18.4 | 0.7 | |
BPA | 2.5 | 4 | 20.6 ± 2.2 | 5.5 ± 0.6 | 7.7 ± 0.5 | 3.8 | 2.7 |
8 | 3 | 18.2 ± 2.9 | 5.3 ± 0.5 | 4.8 ± 0.3 | 3.4 | 3.8 | |
24 | 4 | 8.2 ± 0.8 | 2.3 ± 0.3 | 2.9 ± 0.4 | 3.6 | 2.8 |
Group | n a | Survival Time (Days) | %ILS c | p-Value d | ||
---|---|---|---|---|---|---|
Mean ± SD | Median | 95% CI b | ||||
Untreated | 5 | 30.0 ± 4.0 | 30.0 | 26–34 | - | - |
Neutron only | 4 | 33.0 ± 7.7 | 35.0 | 22–40 | 16.7 | 0.18 |
BNCT using BPA 2.5 h | 6 | 43.0 ± 3.8 | 42.0 | 39–50 | 40.0 | 0.0011 |
BNCT using BPA 8 h | 5 | 40.2 ± 5.6 | 40.0 | 34–48 | 33.3 | 0.0079 |
BNCT using cRGD-MID-AC 2.5 h | 7 | 42.4 ± 8.6 | 43.0 | 32–47 | 43.3 | 0.0033 |
BNCT using cRGD-MID-AC 8 h | 6 | 50.3 ± 26.8 | 38.5 | 27- | 28.3 | 0.0499 |
Group | Physical Dose a (Gy) | Photon-Equivalent Dose b (Gy-Eq) | ||
---|---|---|---|---|
Brain | Tumor | Brain | Tumor | |
Untreated | 0.0 | 0.0 | 0.0 | 0.0 |
Neutron only | 1.6 | 1.6 | 2.6 | 2.6 |
BNCT using BPA 2.5 h | 2.2 | 4.6 | 3.4 | 10.9 |
BNCT using BPA 8 h | 2.2 | 4.2 | 3.3 | 9.9 |
BNCT using cRGD-MID-AC 2.5 h | 1.5 | 2.9 | - * | 5.8 |
BNCT using cRGD-MID-AC 8 h | 1.8 | 4.6 | - * | 9.5 |
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Tsujino, K.; Kashiwagi, H.; Nishimura, K.; Kayama, R.; Yoshimura, K.; Fukuo, Y.; Shiba, H.; Hiramatsu, R.; Nonoguchi, N.; Furuse, M.; et al. Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model. Biology 2023, 12, 377. https://doi.org/10.3390/biology12030377
Tsujino K, Kashiwagi H, Nishimura K, Kayama R, Yoshimura K, Fukuo Y, Shiba H, Hiramatsu R, Nonoguchi N, Furuse M, et al. Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model. Biology. 2023; 12(3):377. https://doi.org/10.3390/biology12030377
Chicago/Turabian StyleTsujino, Kohei, Hideki Kashiwagi, Kai Nishimura, Ryo Kayama, Kohei Yoshimura, Yusuke Fukuo, Hiroyuki Shiba, Ryo Hiramatsu, Naosuke Nonoguchi, Motomasa Furuse, and et al. 2023. "Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model" Biology 12, no. 3: 377. https://doi.org/10.3390/biology12030377
APA StyleTsujino, K., Kashiwagi, H., Nishimura, K., Kayama, R., Yoshimura, K., Fukuo, Y., Shiba, H., Hiramatsu, R., Nonoguchi, N., Furuse, M., Takami, T., Miyatake, S. -I., Hu, N., Takata, T., Tanaka, H., Suzuki, M., Kawabata, S., Nakamura, H., & Wanibuchi, M. (2023). Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model. Biology, 12(3), 377. https://doi.org/10.3390/biology12030377