Clinical review of the japanese experience with boron neutron capture therapy and a proposed strategy using epithermal neutron beams

Abstract

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through 10B(n, alpha)7 Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001. With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15 Gy or, alternatively, a minimum target volume dose of 18 Gy. The maximum vascular dose should not exceed 15 Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10 Gy, including core gamma rays from the reactor and capture gamma in brain tissue. The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

“…No randomized clinical trials addressing BNCT have been carried out, and the prior Phase II trials have addressed BNCT in the treatment of glioblastoma (20,(28)(29)(30)(31)(32). Because sufficient numbers of epithermal neutrons for BNCT can at present only be obtained from a nuclear reactor, availability of BNCT is currently limited to a few centers worldwide.…”

Biomedical applications of10B and11B NMR

“…Boron-containing molecules used in BNCT, most notably BSH and BPA, were investigated by NMR in solution, physiological fluids, cultured cells, laboratory animals, and humans. 10 B and 11 B NMR are sensitive enough to detect these molecules at physiologically relevant concentrations in-vivo, with the possibility of obtaining MR images at about 10 1 mm spatial resolution, under realistic conditions of concentration and scan time. 10 B MRI is a potentially useful tool for improving the clinical efficacy of BNCT, by providing the means for more accurate treatment planning, but its practical utilization still remains to be proven.…”

“…[Reproduced from Bradshaw KM, Schweizer MP, Glover GH, Hadley JR, Tippets R, Tang PP, Davis WL, Heilbrun MP, Johnson S, Ghanem T. BSH distributions in the canine head and a human patient using 11 that study, a range of rotational correlation times was achieved experimentally by dissolving BSH in glycerol and varying the temperature. The single-exponential approximation was also shown to hold for the 10 B relaxation of BSH in a mouse tumor at 4.7 T (21.5 MHz), 39 and the relaxation times were measured to be T 1 ¼ 2.9 AE 0.3 ms and T 2 ¼ 1.75 AE 0.25 ms. Thus, the apparent transverse relaxation rate is slower than that of 11 B under the same circumstances, which was also corroborated by theoretical simulation.…”

“…Experimental measurements yielded values of 5.2 at 4.7 T, and 7.7 at 2.0 T. 40 However, the sensitivity advantage for 1 H is further eroded by various spectral editing procedures that are inevitable in order to distinguish the small 1 H proton signal from BSH from a huge background. Moreover, the much shorter T 1 relaxation time for 10 B permits faster pulse repetition rates, thereby improving the S/N per unit time for 10 B.…”

“…The imaging of 10 B-enriched BSH by 10 B MRI was demonstrated on mice following i.v. injection of the compound.…”