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

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 10B(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. © 2000 Cancer Research Campaig

The role of primordial atmosphere composition in organic matter delivery to early Earth

A model of the atmospheric entry of sub-mm grains is employed to evaluate the effect of the chemical composition of the primordial Earth’s atmosphere on the grain heating, in the context of organic matter delivery. Calculations are performed with spherical, uniform grains of forsterite/fayalite composition as well with the recently proposed white soft mineral (WSM) grains. Different hypotheses on primordial atmosphere composition affect the scale height and the energy transfer. The present work shows that: the total gas budget of the atmosphere is not highly relevant as far as the determination of the heating associated with slowing to subsonic speed is concerned; accordingly, light components (which are expected to be present in a primordial atmosphere and more abundant in the upper one) may be the primary ones in the evaluation of momentum and heat transfer in such scenarios. Strong reduced heating is obtained in the case of an upper atmosphere rich in light components, showing that the composition of the primordial Earth atmosphere may represent the key issue in the delivery of thermolabile organic matter enclosed in sub-mm extraterrestrial grains

Thermal decomposition rate of MgCO3 as an inorganic astrobiological matrix in meteorites

Carbonate minerals, likely of hydrothermal origins and included into orthopyroxenite, have been extensively studied in the ALH84001 meteorite. In this meteorite, nanocrystals comparable with those produced by magnetotactic bacteria have been found into a carbonate matrix. This leads naturally to a discussion of the role of such carbonates in panspermia theories. In this context, the present work sets the basis of a criterion to evaluate whether a carbonate matrix in a meteor entering a planetary atmosphere would be able to reach the surface. As a preliminary step, the composition of carbonate minerals in the ALH84001 meteorite is reviewed; in view of the predominance of Mg in these carbonates, pure magnesite (MgCO3) is proposed as a mineral model. This mineral is much more sensitive to high temperatures reached during an entry process, compared with silicates, due to facile decomposition into MgO and gaseous carbon dioxide (CO2). A most important quantity for further studies is therefore the decomposition rate expressed as CO2 evaporation rate J (molecules/m2 s). An analytical expression for J(T) is given using the Langmuir law, based on CO2 pressure in equilibrium with MgCO3 and MgO at the surface temperature T. Results suggest that carbonate minerals rich in magnesium may offer much better thermal protection to embedded biological matter than silicates and significantly better than limestone, which was considered in previous studies, in view of the heat absorbed by their decomposition even at moderate temperatures. This first study can be extended in the future to account for more complex compositions, including Fe and Ca.I minerali carbonatici, probabilmente di origine idrotermale e inclusi nell'ortopropossenite, sono stati ampiamente studiati nel meteorite ALH84001. In questo meteorite, i nanocristalli paragonabili a quelli prodotti dai batteri magnetotattici sono stati trovati in una matrice carbonatica. Ciò porta naturalmente a una discussione sul ruolo di tali carbonati nelle teorie della panspermia. In questo contesto, il presente lavoro pone le basi di un criterio per valutare se una matrice carbonatica in una meteora che entra in un'atmosfera planetaria sarebbe in grado di raggiungere la superficie. Come fase preliminare, viene rivista la composizione dei minerali di carbonato nel meteorite ALH84001; in considerazione della predominanza di Mg in questi carbonati, la magnesite pura (MgCO3) viene proposta come modello minerale. Questo minerale è molto più sensibile alle alte temperature raggiunte durante un processo di entrata, rispetto ai silicati, a causa della facile decomposizione in MgO e anidride carbonica gassosa (CO2). Una quantità molto importante per ulteriori studi è quindi il tasso di decomposizione espresso come tasso di evaporazione della CO2 J (molecole / m2 s). Un'espressione analitica per J (T) è data usando la legge di Langmuir, basata sulla pressione di CO2 in equilibrio con MgCO3 e MgO alla temperatura superficiale T. I risultati suggeriscono che i minerali di carbonato ricchi di magnesio possono offrire una protezione termica molto migliore alla materia biologica incorporata rispetto a silicati e significativamente migliori del calcare, che era stato considerato in studi precedenti, in considerazione del calore assorbito dalla loro decomposizione anche a temperature moderate. Questo primo studio può essere esteso in futuro per tenere conto di composizioni più complesse, tra cui Fe e Ca