Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors

Author:

Fujikawa Yoshiki1ORCID,Kawabata Shinji1ORCID,Tsujino Kohei1ORCID,Yamada Hironori1,Kashiwagi Hideki1ORCID,Yagi Ryokichi1,Hiramatsu Ryo1ORCID,Nonoguchi Naosuke1,Takami Toshihiro1,Sasaki Akinori2,Hu Naonori2ORCID,Takata Takushi3,Tanaka Hiroki3ORCID,Suzuki Minoru3,Wanibuchi Masahiko1ORCID

Affiliation:

1. Department of Neurosurgery Osaka Medical and Pharmaceutical University Osaka Japan

2. Kansai BNCT Medical Center Osaka Medical and Pharmaceutical University Osaka Japan

3. Institute for Integrated Radiation and Nuclear Science Kyoto University Osaka Japan

Abstract

AbstractMetastatic spinal tumors are increasingly prevalent due to advancements in cancer treatment, leading to prolonged survival rates. This rising prevalence highlights the need for developing more effective therapeutic approaches to address this malignancy. Boron neutron capture therapy (BNCT) offers a promising solution by delivering targeted doses to tumors while minimizing damage to normal tissue. In this study, we evaluated the efficacy and safety of BNCT as a potential therapeutic option for spine metastases in mouse models induced by A549 human lung adenocarcinoma cells. The animal models were randomly allocated into three groups: untreated (n = 10), neutron irradiation only (n = 9), and BNCT (n = 10). Each mouse was administered 4‐borono‐L‐phenylalanine (250 mg/kg) intravenously, followed by measurement of boron concentrations 2.5 h later. Overall survival, neurological function of the hindlimb, and any adverse events were assessed post irradiation. The tumor‐to‐normal spinal cord and blood boron concentration ratios were 3.6 and 2.9, respectively, with no significant difference observed between the normal and compressed spinal cord tissues. The BNCT group exhibited significantly prolonged survival rates compared with the other groups (vs. untreated, p = 0.0015; vs. neutron‐only, p = 0.0104, log‐rank test). Furthermore, the BNCT group demonstrated preserved neurological function relative to the other groups (vs. untreated, p = 0.0004; vs. neutron‐only, p = 0.0051, multivariate analysis of variance). No adverse events were observed post irradiation. These findings indicate that BNCT holds promise as a novel treatment modality for metastatic spinal tumors.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

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