Integrin αvβ3 is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized closo-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin αvβ3 was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin αvβ3 in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA.
Background: Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated. Methods: Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used. TSPO expression was evaluated in the F98 rat glioma model. Boron uptake was assessed in three rat glioma cell lines and in the F98 rat glioma model. In vitro and in vivo neutron irradiation experiments were performed. Results: DPA-BSTPG was efficiently taken up in vitro. The brain tumor has 16-fold higher TSPO expressions than its brain tissue. The compound biological effectiveness value of DPA-BSTPG was 8.43 to F98 rat glioma cells. The boron concentration in the tumor using DPA-BSTPG convection-enhanced delivery (CED) administration was approximately twice as high as using BPA intravenous administration. BNCT using DPA-BSTPG has significant efficacy over the untreated group. BNCT using a combination of BPA and DPA-BSTPG gained significantly longer survival times than using BPA alone. Conclusion: DPA-BSTPG in combination with BPA may provide the multi-targeted neutron capture therapy against HG.
Background: Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation method. High-dose methotrexate and whole-brain radiation therapy (WBRT) are the recommended treatments for primary central nervous system lymphoma (PCNSL). This tumor responds well to initial treatment but relapses even after successful treatment, and the prognosis is poor as there is no safe and effective treatment for relapse. In this study, we aimed to conduct basic research to explore the possibility of using BNCT as a treatment for PCNSL. Methods: The boron concentration in human lymphoma cells was measured. Subsequently, neutron irradiation experiments on lymphoma cells were conducted. A mouse central nervous system (CNS) lymphoma model was created to evaluate the biodistribution of boron after the administration of borono-phenylalanine as a capture agent. In the neutron irradiation study of a mouse PCNSL model, the therapeutic effect of BNCT on PCNSL was evaluated in terms of survival. Results: The boron uptake capability of human lymphoma cells was sufficiently high both in vitro and in vivo. In the neutron irradiation study, the BNCT group showed a higher cell killing effect and prolonged survival compared with the control group. Conclusions: A new therapeutic approach for PCNSL is urgently required, and BNCT may be a promising treatment for PCNSL. The results of this study, including those of neutron irradiation, suggest success in the conduct of future clinical trials to explore the possibility of BNCT as a new treatment option for PCNSL.
Background: Neuronavigation systems have become essential tools in image-guided neurosurgery that aid in the accurate resection of brain tumors. Recent advancements to these devices can indicate the precise location of lesions but can also project an augmented reality (AR) image on the microscope eyepiece to facilitate a successful surgical operation. Although the transcortical approach is a very popular method in neurosurgery, it can lead to disorientation and can cause unnecessary brain damage when the distance from the brain surface to the lesion is long. Herein, we report on an actual case in which a virtual line from AR images was used to assist the transcortical approach. Methods: A virtual line connecting the entry point and the target point, which were set as the navigation route, was created using Stealth station S7® (Medtronic, Minneapolis, USA). This line was projected as an AR image on the microscope eyepiece. It was possible to reach the target point by proceeding through the white matter along the displayed virtual line. Results: The lesion was reached within a short duration using virtual line without disorientation. Conclusion: Setting a virtual line as an AR image using neuronavigation is a simple and accurate method that can effectively support the conventional transcortical approach.
Symptomatic unruptured intracranial aneurysms, particularly blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA), can present with severe pain indicating impending rupture and pose significant treatment challenges. We present the case of a 40-year-old man with sudden onset severe headache and deep orbital pain (DOP) caused by an unruptured ICA BBA confirmed via angiography. Given the aneurysm's morphology and the patient's escalating symptoms despite analgesia, emergent endovascular treatment with a flow diverter (FD) was performed. This intervention resulted in immediate and complete resolution of the patient's debilitating pain, followed by successful aneurysm occlusion confirmed at six-month follow-up. This case highlights the potential efficacy of FD placement not only for aneurysm obliteration but also for rapid symptom relief in patients with high-risk, symptomatic unruptured BBAs.