論文 - 詳細
| RRC ID | 78704 |
|---|---|
| 著者 | Watanabe T, Yoshikawa T, Tanaka H, Kinashi Y, Kashino G, Masunaga SI, Hayashi T, Uehara K, Ono K, Suzuki M. |
| タイトル | Pharmacokinetic Study of 14C-Radiolabeled p-Boronophenylalanine (BPA) in Sorbitol Solution and the Treatment Outcome of BPA-Based Boron Neutron Capture Therapy on a Tumor-Bearing Mouse Model. |
| ジャーナル | Eur J Drug Metab Pharmacokinet |
| Abstract |
BACKGROUND AND OBJECTIVE:Boron neutron capture therapy (BNCT) is a binary cancer treatment that combines boron administration and neutron irradiation. The tumor cells take up the boron compound and the subsequent neutron irradiation results in a nuclear fission reaction caused by the neutron capture reaction of the boron nuclei. This produces highly cytocidal heavy particles, leading to the destruction of tumor cells. p-boronophenylalanine (BPA) is widely used in BNCT but is insoluble in water and requires reducing sugar or sugar alcohol as a dissolvent to create an aqueous solution for administration. The purpose of this study was to investigate the pharmacokinetics of 14C-radiolabeled BPA using sorbitol as a dissolvent, which has not been reported before, and confirm whether neutron irradiation with a sorbitol solution of BPA can produce an antitumor effect of BNCT. MATERIALS AND METHODS:In this study, we evaluated the sugar alcohol, sorbitol, as a novel dissolution aid and examined the consequent stability of the BPA for long-term storage. U-87 MG and SAS tumor cell lines were used for in vitro and in vivo experiments. We examined the pharmacokinetics of 14C-radiolabeled BPA in sorbitol solution, administered either intravenously or subcutaneously to a mouse tumor model. Neutron irradiation was performed in conjunction with the administration of BPA in sorbitol solution using the same tumor cell lines both in vitro and in vivo. RESULTS:We found that BPA in sorbitol solution maintains stability for longer than in fructose solution, and can therefore be stored for a longer period. Pharmacokinetic studies with 14C-radiolabeled BPA confirmed that the sorbitol solution of BPA distributed through tumors in much the same way as BPA in fructose. Neutron irradiation was found to produce dose-dependent antitumor effects, both in vitro and in vivo, after the administration of BPA in sorbitol solution. CONCLUSION:In this report, we demonstrate the efficacy of BPA in sorbitol solution as the boron source in BNCT. |
| 巻・号 | 48(4) |
| ページ | 443-453 |
| 公開日 | 2023-7-1 |
| DOI | 10.1007/s13318-023-00830-y |
| PII | 10.1007/s13318-023-00830-y |
| PMID | 37198368 |
| MeSH | Animals Boron Boron Neutron Capture Therapy* / methods Fructose Mice Sorbitol Treatment Outcome |
| リソース情報 | |
| ヒト・動物細胞 | SAS(RCB1974) |