Indication of boron neutron capture therapy based on 18F-labeled BPA positron emission tomography of individual patients: New indications and possibility for other brain malignancies
Authors: Shinji Kawabata, Kyoko Iida, Shin-Ichi Miyatake, Naosuke Nonoguchi, Minoru Miyashita, Toshihiko Kuroiwa, Yoshio Imahori, Koji Ono
Journal: Clinical Cancer Research (2007)

B26  Boron neutron capture therapy (BNCT) is cell selective particle irradiation based upon the nuclear reaction that occur when non-radioactive boron-10 (10B) is irradiated with low energy neutrons to produce high energy alpha particles (10B[n,alpha] 7Li). In order for BNCT to be successful, a sufficient amount of 10B and neutrons must be delivered to the tumor. We have treated a group of 50 patients with high grade gliomas using a combination of surgery followed by BNCT. Our modified BNCT was carried out at the Kyoto University Research Reactor Institute (KURRI) using an epithermal neutron beam together with use of two different boron drugs, sodium borocaptate (BSH) and boronophenylalanine (BPA), both of which have been used clinically. Successful BNCT depends on the distribution of boron containing drugs in both tumor and normal tissue. BPA is accumulated depends on the tumor metabolism of amino acids and it is variable in each cases. Recently, we used 18F-labeled BPA positron emission tomography (PET) for almost all the patients who will receive BNCT and irradiation dose was calculated from tumor to normal brain (T/N) ratio from BPA-PET and blood sampling [presented at the last meeting]. Analyze the drug accumulation prior to individual treatment was useful for think about therapy effect and for reduce side effect. This time, we also discuss about usefulness of BPA-PET for indications of this treatment.  Malignant meningiomas, similar to glioblastomas, are difficult tumors to control because of its infiltrative nature. There have been numerous studies on the treatment of malignant meningioma by means of external beam radiation therapy, and although there is convincing evidence that such treatment can provide effective palliation of neurologic symptoms, as well as modest increases in life span, cures have been rare. Recently, 10 patients with recurrent malignant meningioma were treated by BNCT using BPA and BSH as the capture agent between 2005 and 2007 at Osaka Medical College. Seven patients who underwent BPA-PET analysis showed good BPA uptake, with a greater than 2.7 T/N ratio and the estimated maximum dose delivered to residual tumor was from 55 to 144.8 Gy-Eq and to normal brain was less than 14.6 Gy-Eq. All patients had previously undergone repetitive surgeries and radiotherapy, however, they have demonstrated radiographically decrease in the volume and improvement of their neurological symptoms. One atypical meningioma case showed a low T/N ratio of 2.0 and maximum tumor dose was 49 Gy-Eq and showed normal brain damage without significant effect. Indication of BNCT was based on their high uptake of boron drug (BPA) resulted from BPA-PET study and malignant meningiomas seem to be good candidates for BNCT.  We found some other intracranial malignancies such as malignant lymphoma and brain metastasis showed high T/N ratios. They are usually treated with radiation and chemotherapy; however, therapy for the recurrent disease after irradiation is sometimes difficult. Therefore, BNCT, cell selective irradiation, have a possibility of indication to such situations. This concept is already indicated for the extra cranial malignancies, head and neck, malignant melanoma, lung and liver cancers.