悪性グリオーマに対する中性子捕捉療法における硼素化合物(BSH : Na2B12H11SH)の薬物動態と腫瘍内移行

BNCT (boron neutron capture therapy) is based on the intracellular nuclear reaction that occurs between the boron-10 nucleus and a thermal neutron. Upon capture, the boron nucleus disintegrates into highly energetic alpha (4He) and lithium (7Li) particles. Because of the short pathways of these heavy particles and 10B accumulation in target tissues, the great potential advantage of BNCT is a selective tumor destruction without significant damage to normal brain tissue.
Since 1968, we have treated 146 patients with malignant brain tumors by BNCT. The 5-year survival rate of malignant glioma was 29%. Important factors which improve the results of BNCT are boron concentration in the tumor and neutron sauces.
We have used BSH (mercaptoundecahydrododecaborate, Na2B12H11SH) as a boron compound in all patients. BSH is characterized by the absence of toxic side effects and represents the only promising boron carrier applied for the therapy of malignant glioma. However, data on the biodistribution and pharmacokinetics of BSH are few and lack in stadardization. We retrospectively analyzed the biodistribution and pharmacokinetics of BSH in 146 patients treated by BNCT from 1968 to 1994.
1) Pharmacokinetic parameters and standard expression of blood boron content of BSH were calculated by the two-compartment model theory in intra-arterial and intra-venous infusion groups. The parameters revealed that BSH could move easily from blood to the peripheral organs with sustained retention and that elimination was very slow. (CL=3.43L/hr, Vss=181.8 L, MRT=53.0 hrs)
2) Pharmacokinetic parameters were calculated in each case. The patients were divided into two groups : the intra-arterial (56 patients) and the intra-venous (31 patients) groups. BSH was administered into cervical brain arteries in the intra-arterial group, and peripheral veins in the intra-venous group. BSH in the intra-arterial infusion group was found to move from blood into the peripheral organs more easily than that of the intravenous infusion group.
3) In patients with malignant glioma, the average values of boron concentration in the tumor and the tumor to blood ratio (T /B ratio) after intra-arterial infusion (44 patients with 53 samples) were 26.8 μg/g and 1. 77 respectively. On the other hand, after intravenous infusion (13 patients with 13 samples) the values were 20. 9 μg/ g and 1. 33 respectively. There were no statistical significant differences in the average values of boron concentration in the tumor and the T /B ratio between the intra-arterial and the intravenous groups.
4) Both the average values of boron concentration in the tumor and the T /B ratio in patients with malignant glioma showed about 2. 7 and 3. 0 times higher that those of low grade glioma. However, there were no statistical significant differences in the tumoral boron concentration and the T /B ratio between cases of anaplastic astrocytoma and glioblastoma.