Boron Neutron Capture Therapy of Malignant Melanoma Using 10 B-Paraboronophenylalanine with Special Reference to Evaluation of Radiation Dose and Damage to the Normal Skin

Fukuda, Hiroshi; Hoshino, Junichi; Honda, C.; Kobayashi, Tooru; Yoshino, Kazuo; Karashima, Hiroshi; Takahashi, Jutaro; Abe, Yoshinao; Kanda, Keiji; Ichihashi, Masamitsu; Mishima, Yutaka

doi:10.2307/3578693

Cited by 98 publications

(56 citation statements)

References 18 publications

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“…The values were among 3 and 9 ppm of boron in blood. 13 The concentration of 10 ppm of boron in the medium of cells cultures adopted in our study represents a value close to those above mentioned values determined in blood samples during clinical treatments.…”

Section: Methodssupporting

confidence: 88%

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

Portu

Rossini

Gadan

et al. 2016

Reports of Practical Oncology & Radiotherapy

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Section: Methodssupporting

confidence: 88%

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

Portu

Rossini

Gadan

et al. 2016

Reports of Practical Oncology & Radiotherapy

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“…In this paper, we described the procedures for our BNCT of the malignant melanoma based on the pharmacokinetics of BPA and radiobiological considerations [9][10][11] . Although the same logical procedures for dose optimization were performed, the radiation doses to the normal skin varied considerably and exceeded the maximum tolerance limits in some cases.…”

Section: Discussionmentioning

confidence: 99%

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

Fukuda

Hoshino

Kobayashi

et al. 2003

Australas. Phys. Eng. Sci. Med.

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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.

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“…For thermal beams, RBE values in the range 2.7-3.9 have been documented (Yamamoto, 1961;Archambeau, 1989;Morris et al, 1994). A CBE factor of ~2.5 has been estimated for both hamster and human skin using BPA as the boron delivery agent (Hiratsuka et al, 1991;Fukuda et al, 1994). A higher CBE estimate for BPA of ~3.7 was reported using rat skin (Morris et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

et al. 2000

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Summary Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 ( 10 B) in the oral mucosa to the biological effectiveness of the 10 B(n,α) 7 Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10 B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10 B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10 B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10 B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10 B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10 B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10 B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 ± 0.02. This compares with a previously published CBE factor for BPA of 4.87 ± 0.16. It was concluded that variations in the microdistribution profile of 10 B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiationinduced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10 B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT.

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Boron Neutron Capture Therapy of Malignant Melanoma Using 10 B-Paraboronophenylalanine with Special Reference to Evaluation of Radiation Dose and Damage to the Normal Skin

Cited by 98 publications

References 18 publications

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

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

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

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