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

Journal Article · Thu May 04 00:00:00 EDT 2000 · British Journal of Cancer

DOI:https://doi.org/10.1054/bjoc.2000.1148· OSTI ID:2470271

Morris, G. M. ^[1]; Smith, D. R. ^[2]; Patel, H. ^[1]; Chandra, S. ^[2]; Morrison, G. H. ^[2]; Hopewell, J. W. ^[1]; Rezvani, M. ^[1]; Micca, P. L. ^[3]; Coderre, J. A. ^[3]

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1. Univ. of Oxford (United Kingdom)
2. Cornell Univ., Ithaca, NY (United States)
3. Brookhaven National Laboratory (BNL), Upton, NY (United States)

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 (¹⁰B) in the oral mucosa to the biological effectiveness of the ¹⁰BB(n,α)⁷Li 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. ¹⁰B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of ¹⁰B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood ¹⁰B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The ¹⁰B 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 ¹⁰B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of ¹⁰B 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 ¹⁰B 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 ¹⁰B, 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 radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of ¹⁰B 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.

• Research Organization: Brookhaven National Laboratory (BNL), Upton, NY (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: AC02-98CH10886; SC0012704
• OSTI ID: 2470271
• Journal Information: British Journal of Cancer, Journal Name: British Journal of Cancer Journal Issue: 11 Vol. 82; ISSN 1532-1827
• Publisher: Springer Nature
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
borocaptate sodium
compound biological effectiveness factor
ion microscopy imaging
oncology
p-boronophenylalanine
rat ventral tongue mucosa