Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as ¹⁰B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient ¹⁰B concentration within tumors. To address the issue of ¹⁰B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that ¹⁰B-MMT1242 is a candidate for further clinical BNCT studies.

Boron neutron capture therapy (BNCT) is a cancer treatment with clinically demonstrated efficacy using boronophenylalanine (BPA) and sodium mercaptododecaborate (BSH). However, tumor tissue selectivity of BSH and retention of BPA in tumor cells is a constant problem. To ensure boron accumulation and retention in tumor tissues, we designed a novel polyethylene glycol (PEG)-based boron-containing lipid (PBL) and examined the potency of delivery of boron using novel PBL-containing liposomes, facilitated by the enhanced permeability and retention (EPR) effect. PBL was synthesized by the reaction of distearoylphosphoethanolamine and BSH linked by PEG with Michael addition while liposomes modified using PBL were prepared from the mixed lipid at a constant molar ratio. In this manner, novel boron liposomes featuring BSH in the liposomal surfaces, instead of being encapsulated in the inner aqueous phase or incorporated in the lipid bilayer membrane, were prepared. These PBL liposomes also carry additional payload capacity for more boron compounds (or anticancer agents) in their inner aqueous phase. The findings demonstrated that PBL liposomes are promising candidates to effect suitable boron accumulation for BNCT.

We report a case of a holocord high-intensity lesion extending from L1 up to the medulla oblongata on T2-weighted spinal magnetic resonance imaging (MRI) associated with an intramedullary spinal abscess secondary to an infected dermoid cyst. The intraoperative findings revealed that the high-intensity lesion on the T2-weighted image was edematous tissue. The MRI change in the spinal cord gradually improved in response to the use of postoperative antibiotics. The change was considered to represent reversible inflammatory changes, as there was no neurological deficit found at the cervical level and it resolved after surgery and medical treatment. The pathomechanism is discussed herein.

Introduction: Quadrigeminal arachnoid cyst (QAC) associated with encephalocele is rare; and while some treatments have been developed in recent years, no definite therapeutic approach for QAC has been established. Endoscopic treatment for arachnoid cyst is gaining popularity because it is relatively less invasive to the normal brain tissues. Case presentation: The patient, a 4-year-old girl, presented with QAC associated with congenital occipital encephalocele. At the age of 1 month, repair of the perinatal encephalocele had been performed at another institute. An asymptomatic arachnoid cyst remained in the posterior fossa, which was closely monitored with follow up. At age 4 years, the patient started to complain of headache, which gradually increased in both strength and frequency. Magnetic resonance imaging (MRI) revealed cerebellar compression due to cyst enlargement. We performed neuroendoscopic cyst fenestration with an occipital bone approach. Post-operative MRI showed reduced size of the cyst, and the headache dramatically improved and resolved. Discussion: The standard treatment of QAC is still controversial; however, our successful use of endoscopic fenestration toward the third ventricle indicates its efficacy and safety. QACs have been classified into 3 types based on their expansion mechanisms; our case might suggest another possible mechanism of QAC development. Conclusion: In our case, endoscopic cyst fenestration was successful for QAC with perinatal encephalocele. However, long-term follow-up and analysis of similar cases are needed to determine its effectiveness.

Expansion of preoperative edema (PE) is an independent poor prognostic factor in high-grade gliomas. Evaluation of PE provides important information that can be readily obtained from magnetic resonance imaging (MRI), but there are few reports on factors associated with PE. The goal of this study was to identify factors contributing to PE in Grade 3 (G3) and Grade 4 (G4) gliomas. PE was measured in 141 pathologically proven G3 and G4 gliomas, and factors with a potential relationship with PE were examined in univariate and multivariate analyses. The following eight explanatory variables were used: age, sex, Karnofsky performance status (KPS), location of the glioma, tumor diameter, pathological grade, isocitrate dehydrogenase (IDH)-1-R132H status, and Ki-67 index. Overall survival (OS) and progression-free survival (PFS) were calculated in groups divided by PE (<1 vs. ≥1 cm) and by factors with a significant correlation with PE in multivariate analysis. In univariate analysis, age (p = 0.013), KPS (p = 0.012), pathology grade (p = 0.004), and IDH1-R132H status (p = 0.0003) were significantly correlated with PE. In multivariate analysis, only IDH1-R132H status showed a significant correlation (p = 0.036), with a regression coefficient of -0.42. The median follow-up period in survivors was 38.9 months (range: 1.2-131.7 months). The one-, two-, and three-year OS rates for PE <1 vs. ≥1 cm were 77% vs. 68%, 67% vs. 44%, and 63% vs. 24% (p = 0.0001), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 67%, 85% vs. 40%, and 81% vs. 21% (p < 0.0001), respectively. The one-, two-, and three-year PFS rates for PE <1 vs. ≥1 cm were 77% vs. 49%, 64% vs. 24%, and 50% vs. 18% (p = 0.0002), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 48%, 77% vs. 23%, and 73% vs. 14% (p < 0.0001), respectively. IDH1-R132H status was found to be a significant contributor to PE. Cases with PE <1 cm and those with the IDH1-R132H mutation clearly had a better prognosis.