The use of heavy water in boron neutron capture therapy of brain tumours

Abstract

A theoretical analysis is presented from which it is concluded that transient partial deuteration of body water for neutron capture therapy would significantly enhance radiation produced by the neutron-boron reaction at the deep margins of brain tumours and reduce effective gamma radiation to normal brain tissues by 50% or more. The analysis deals only with totally thermalised incident neutrons.

Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

“…Many approaches have been devised to investigate the interaction of neutron beams with the human brain. There are the Monte-Carlo (MC) simulations conducted with three-dimensional ellipsoid geometries (Wallace et al 1995a), the bi-dimensional transport model (Matsumoto 1990), and simpler linear transport calculations (Slatkin et al 1983a). The MC approach is the most thorough, employing two three-dimensional ellipsoids that describe the skull and brain volumes.…”

“…Finally, linear transport calculations are sufficiently simple to consider here without detracting from the qualitative estimation of oedema impact on a neutron flux and its interaction with a target, e.g., the human brain or a water sample. Slatkin et al derived in detail the equations for simple linear transport calculations (Slatkin et al 1983a). For simplicity, these calculations are based on a semiinfinite body-referred herein as a phantom-that contains 100% water and has a thickness D = 16 cm.…”

“…(3) Equation ( 3) describes the dependence of the thermal neutron flux attenuation coefficient on deuterated water (Slatkin et al 1983a). A correction, ξ , for the thermal-neutron irradiation enhancement factor can be calculated according to equation (4).…”

“…Deuterium affects, in various ways, the blood, the thymus, the bone marrow and the lymphoid tissue (Hodel et al 1982, Joenje et al 1983, Adams and Adams 1988, Laissue and Stoner 1979, Laissue and Slatkin 1976. More recently, a new interest in this isotope has emerged because its reduced thermal neutron capture cross-section could enhance boron neutron capture therapy (BNCT) of glioblastoma multiforme (GBM: grade IV astrocytoma) (Slatkin et al 1983a, 1983b, Kiszenick et al 1984, Sakurai 2004, Wallace et al 1995a, 1995b. BNCT requires that (1) the administered boronated compound accumulates in sufficiently high concentrations at the tumour locus and (2) an appropriately thermalized neutron flux reaches the boronated target molecules (Coderre 1998, Hatanaka 1989, 1991, Diaz et al 2000, Coderre and Morris 1999, Chanana et al 1999, Matsumoto 1990).…”

“…Boron ( 10 B) atoms capture incoming neutrons at the tumour locus and form an unstable species that undergo α-decay to 7 Li, 10 B(n, α) 7 Li, depositing 2.31 MeV within 10-15 µm of tissue parenchyma. The major limitations of this technique, however, are the excessive moderation of incoming neutrons via elastic scattering with and the large thermal neutron capture crosssection of protons, which not only reduce the number of neutrons reaching the boronated target molecules but also increase the recoil γ -radiation dose deposition from the proton capture reaction, 1 H(n,γ ) 2 H. Since most soft tissue protons are found in the bulk water phase, neutron beam attenuation and γ -radiation dose deposition can be minimized via extensive deuteration of body fluids (Slatkin et al 1983a, 1983b, Kiszenick et al 1984, Sakurai 2004, Wallace et al 1995a, 1995b. Furthermore, partial deuteration of the internal milieu increases neutron flux homogeneity and diminishes the formation of local 'hot-spots', thus allowing for the delivery of larger radiation doses to tumour cells while simultaneously preserving the integrity of healthy tissue (Wallace et al 1995a(Wallace et al , 1995b.…”