**4. Future development of BNCT**

At our institution, we have previously performed a clinical trial of reactor BNCT even for high-grade meningiomas and reported the results of BNCT for recurrent meningiomas [16, 17]. Prior to the treatment, 18F-labeled BPA positron emission tomography (FBPA- PET) was performed using a therapeutic agent, boron compound BPA, labeled with 18F as a tracer, and the tumor-to-normal brain (Tumor/Normal: T/N) ratio averaged 3.8. This value is equal to or better than the value experienced in glioma. The introduction of this PET study proved to be useful for the treatment of recurrent malignant glioma, but it was also indispensable for developing nuclear reactor BNCT for cancers of other organs of the whole body, as well as for the later expansion of indications for head and neck cancer. In high-grade meningiomas, although there was transient enhancement of contrast areas (pseudoprogression) in a few cases, all cases showed a reduction in tumor volume. These were all patients with recurrence after multiple surgeries and radiotherapy, and the treatment outcome after BNCT was generally good, but they are rare tumors, and there are few consolidated reports that can be compared. The major cause of death was metastasis to the whole

### **Figure 5.**

*A case of high-grade meningioma treated with reactor-based BNCT with significant response. The tumor in this case was located in the midline and was a recurrent case of refractory skull base meningioma, although a shrinkage effect was observed. (left: FBPA-PET fusion, middle: Before treatment, right: After BNCT of contrastenhanced MRI T1WI).*

*Boron Compounds for Neutron Capture Therapy in the Treatment of Brain Tumors DOI: http://dx.doi.org/10.5772/intechopen.106202*

#### **Figure 6.**

*Contrast-enhanced MRI compared with 18FBPA PET in malignant glioma (left: FBPA-PET fusion, right: Contrast-enhanced MRI T1WI) BNCT uses biological targets and does not cause irradiation of any unnecessary sites because there is no confusion in setting the radiation field. The irradiation field is defined by the boron distribution, and there is no need for the physician to set the borders of the irradiation field.*

body, in addition to seeding cancer cells into the cerebrospinal fluid cavity, with good local control of the irradiated area.

Subsequent analysis showed that the method was effective in deep-seated tumors such as the skull base, where the dose is very low (**Figure 5**) [18]. The therapeutic effects of these cases treated using reactors have led to the development of physicianled clinical trials using accelerator-based neutron sources.

Even in situations where nuclear reactors have to be used as neutron sources, proposals for new indications and improved protocols have resulted in better treatment outcomes, and BNCT research has not been interrupted until now since the beginning of clinical research in the 1960s. Under such circumstances, Japan succeeded in BNCT using an accelerator-type neutron generator for the first time in the world [13]. Recently, the attention that exceeds the academic interest from all fields and industries around the world has also increased in keeping with the success of Japan. In the field of brain tumors, global standards are expected to be challenged in the future, such as

in combination with standard treatments for new diagnostic cases of glioma. However, improvements in the peripheral environment, such as the worldwide spread of approved devices and the approval of unapproved devices for medicine, are also awaited.

The "treatable" intracranial diseases on BNCT range widely and are absolutely not limited to gliomas. However, diseases such as "BNCT can be expected" are limited. In BNCT, it is one of the most important conditions for boron to maintain contrast with normal tissue and sufficiently accumulate in the tumor, and it is necessary to confirm that the boron drug to be administered shows high accumulation in the tumor using some technique before neutron irradiation. In the nuclear reactor BNCT, as described above, attempts to use PET examination with 18 FBPA have preceded, and clinical research has been conducted as "visible drug" (**Figure 6**). Although this idea is a pioneer in the field of "theranostics" that has been promoted recently, it is expected to expand the application of these combinations to new diseases and to tailor-made BNCT treatment.
