Objectives Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when nonradioactive Boron-10 is irradiated with low-energy neutrons to produce high-energy α particles (10B [n, α] 7Li). Possible complications associated with extended surgical resection render high-grade meningioma (HGM) a challenging pathology and skull-base meningiomas (SBMs) even more challenging. Lately, we have been trying to control HGMs using BNCT. This study aims to elucidate whether the recurrence and outcome of HGMs and SBMs differ based on their location. Design Retrospective review. Setting Osaka Medical College Hospital and Kyoto University Research Reactor Institute. Participants Between 2005 and 2014, 31 patients with recurrent HGM (7 SBMs) were treated with BNCT. Main Outcome Measures Overall survival and the subgroup analysis by the anatomical tumor location. Results Positron emission tomography revealed that HGMs exhibited 3.8 times higher boron accumulation than the normal brain. Although tumors displayed transient increases in size in several cases, all lesions were found to decrease during observation. Furthermore, the median survival time of patients with SBMs post-BNCT and after being diagnosed as high-grade were 24.6 and 67.5 months, respectively (vs non-SBMs: 40.4 and 47.5 months). Conclusions BNCT could be a robust and beneficial therapeutic modality for patients with high-grade SBMs.

The effect of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on human oral squamous cell carcinoma (SCC) xenografts in nude mice was examined. Tumor-bearing mice were given BPA at a dose of 250 mg/kg body weight. The tumor (10)B concentration 2 h after an injection of BPA was higher than those 1 or 3 h after the injection. Neutron irradiation was performed beginning 1, 2 or 3 h after an injection of BPA and the effects on body weight of the animals, tumor growth, survival of tumor-bearing animals, and histology of tumor and normal tissue were examined. Fragmented nuclear DNA, 5-bromo-2'-deoxyuridine (BrdU), and von Willebrand Factor (vWF) were detected by immunohistochemical staining. Tumor volumes of untreated control animals increased continuously, whereas those of BNCT-treated animals were markedly decreased. Animals given neutron irradiation 2 h after the injection of BPA survived for a longer period as compared with those given neutron irradiation 1 or 3 h after the injection. BNCT reduced the incorporation of BrdU into tumor cells, and induced the enlargement and vacuolation of tumor cells. Disintegration of blood vessels and dense inflammatory cell infiltration were also observed in the stroma of the tumor, but not surrounding normal tissues. These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.

New carborane-bearing hydroxamate matrix metalloproteinase (MMP) ligands have been synthesized for boron neutron capture therapy (BNCT) with nanomolar potency against MMP-2, -9 and -13. New analogs are based on MMP inhibitor CGS-23023A, and two previously reported MMP ligands 1 (B1) and 2 (B2) were studied in vitro for BNCT activity. The boronated MMP ligands 1 and 2 showed high in vitro tumoricidal effects in an in vitro BNCT assay, exhibiting IC₅₀ values for 1 and 2 of 2.04 × 10⁻² mg/mL and 2.67 × 10⁻² mg/mL, respectively. The relative killing effect of 1 to L-boronophenylalanine (BPA) is 0.82/0.27 = 3.0, and that of 2 is 0.82/0.32 = 2.6, whereas the relative killing effect of 4 is comparable to boronophenylalanine (BPA). The survival fraction of 1 and 2 in a pre-incubation boron concentration at 0.143 ppm ¹⁰B and 0.101 ppm ¹⁰B, respectively, were similar, and these results suggest that 1 and 2 are actively accumulated through attachment to the Squamous cell carcinoma (SCC)VII cells. Compounds 1 and 2 very effectively killed glioma U87 delta EGFR cells after BNCT. This study is noteworthy in demonstrating BNCT efficacy through binding to MMP enzymes overexpressed at the surface of the tumor cell without tumor cell penetration.