Boron neutron capture therapy (BNCT) for malignant melanoma with special reference to absorbed doses to the normal skin and tumor

Abstract

Twenty-two patients with malignant melanoma were treated with boron neutron capture therapy (BNCT) using 10B-p-boronophenylalanine (BPA). The estimation of absorbed dose and optimization of treatment dose based on the pharmacokinetics of BPA in melanoma patients is described. The doses of gamma-rays were measured using small TLDs of Mg2SiO4 (Tb) and thermal neutron fluence was measured using gold foil and wire. The total absorbed dose to the tissue from BNCT was obtained by summing the primary and capture gamma-ray doses and the high LET radiation doses from 10B(n, alpha)7Li and 14N(n,p)14C reactions. The key point of the dose optimization is that the skin surrounding the tumour is always irradiated to 18 Gy-Eq, which is the maximum tolerable dose to the skin, regardless of the 10B-concentration in the tumor. The neutron fluence was optimized as follows. (1) The 10B concentration in the blood was measured 15-40 min after the start of neutron irradiation. (2) The 10B-concentration in the skin was estimated by multiplying the blood 10B value by a factor of 1.3. (3) The neutron fluence was calculated. Absorbed doses to the skin ranged from 15.7 to 37.1 Gy-Eq. Among the patients, 16 out of 22 patients exhibited tolerable skin damage. Although six patients showed skin damage that exceeded the tolerance level, three of them could be cured within a few months after BNCT and the remaining three developed severe skin damage requiring skin grafts. The absorbed doses to the tumor ranged from 15.7 to 68.5 Gy-Eq and the percentage of complete response was 73% (16/22). When BNCT is used in the treatment of malignant melanoma, based on the pharmacokinetics of BPA and radiobiological considerations, promising clinical results have been obtained, although many problems and issues remain to be solved.

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA‐3 reactor in Argentina

“…20,26,27 Figure 3 (a) shows that the average absolute value of the boron concentration in blood for the animal model 60 min after the end of infusion is 18.9 ± 0.6 µg/g, very similar to the one observed in humans. Moreover, the pharmacokinetic model parameters for measured blood in the sheep of k 1 = 0.022 ± 0.008 min −1 , k 2 = 0.012 ± 0.002 min −1 , k 3 = 0.007 ± 0.002 min −1 , and V = 0.247±0.048 (kg/kg) agree well quantitatively with the human data from Kiger et al 22 Lung-to-blood and skin-to-blood boron concentration ratios of 1.3 ± 0.1 and 1.9 ± 0.1 are observed 80 min after EOI [ Fig.…”

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

“…In a study carried out by Fukuda et al ., 16 of 22 patients who received BNCT showed a complete response (12). In 2004, the first case of malignant melanoma treated by BNCT was reported in Argentina, and 21 of the 25 treated subcutaneous melanoma nodules showed complete response 8 weeks after the treatment (11).…”

“…(11) and Fukuda et al . (12), the maximum dose of skin was 16.5 relative biological effectiveness (RBE) Gy and a minimum dose for tumor control was 20 RBE Gy. The irradiation time was calculated by the Monte Carlo N Particle Transport Code 6 (MCNP 6) program, based on the maximum radiation dose of skin, thermal neutron beam flux of IHNI, boron concentration in blood, and ratio value of T/B and N/B measured during the boron pharmacokinetics test.…”

Pioneering and Fundamental Achievements on the Development of Positron Emission Tomography (PET) in Oncology

“…The range of high LET α particle is only approximately 10 µm, which is comparable to the diameter of a cell, therefore, thermal neutron irradiation causes substantial damage limited to cells that take up the tumor-seeking 10 B-compound. Mishima and Fukuda et al initiated a clinical trial of BNCT for malignant melanoma with successful results (Mishima et al 1989a, b;Fukuda et al 1989Fukuda et al , 1999Fukuda et al , 2003. However, 10 B-concentrations in both the tumor and normal tissues could not be directly measured during neutron irradiation, which cause an inaccurate estimation of radiation dose.…”