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

Clinical studies of the treatment of glioma and cutaneous melanoma using bo ron neutron capture therapy (BNCT) are currently taking place in the USA, E urope and Japan. New BNCT clinical facilities are under construction in Fin land, Sweden, England and California The observation of transient acute eff ects in the oral mucosa of a number of glioma patients involved in the Amer ican clinical trials, suggests that radiation damage of the oral mucosa cou ld 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 rela te the microdistribution of boron-10 (B-10) in the oral mucosa to the biolo gical effectiveness of the B-10(n,alpha)Li-7 neutron capture reaction in th is tissue. The two boron delivery agents used clinically in Europe/Japan an d the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respec tively, were evaluated using a rat ventral tongue model. B-10 concentration s in various regions of the tongue mucosa were estimated using ion microsco py. In the epithelium, levels of B-10 were appreciably tower after the admi nistration of BSH than was the case after BPA. The epithelium:blood B-10 pa rtition ratios were 0.2:1 and 1:1 far BSH and BPA respectively. The B-10 co ntent 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 B-10 l evels were a factor of six higher in the lamina propria than in the epithel ium. The concentration of B-10 was also measured in blood vessel walls wher e relatively low levels of accumulation of BSH, as compared with BPA, was d emonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood B-10 partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively Ev aluation of tongue mucosal response (ulceration) to BNC irradiation indicat ed a considerably reduced radiation sensitivity using BSH as the boron deli very agent relative to BPA. The compound biological effectiveness (CBE) fac tor 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 varia tions in the microdistribution profile of B-10, using the two boron deliver y agents, had a significant effect on the response of oral mucosa to BNC ir radiation. From a clinical perspective, based on the findings of the presen t study, it is probable that potential radiation-induced oral mucositis wil l be restricted to BNCT protocols involving BPA. However, a thorough high r esolution analysis of B-10 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. (C) 2000 Cancer Resear ch Campaign.