Gadolinium neutron capture

Martin, RF; Whittaker, A; Cunha, GD; Haigh, A; Pardee, M; Allen, BJ; Kelly, DP

Gadolinium neutron capture

Date

1989-09-22

Authors

Publisher

AINSE

Abstract

The potential for exploitation of the 10B-neutron capture (NC) reaction for cancer therapy has been recognised for some time. The thermal neutron capture cross-section for 10B is much higher than that for the nuclides prevalent in biological material. Moreover the 10B-NC reaction results in fission to form an alpha particle and 7Li atom, each with a range of the order of a cell diameter. Thus the concept of boron neutron capture therapy (BNCT) depends on the use of 10B-labelled Pharmaceuticals that can be delivered preferentially to tumour cells, relative to normal cells in the neutron irradiation field. In the development of the rationale for BNCT, nuclides with higher thermal neutron capture cross sections than 10B (eg. 157Gd, 113cd) were considered inappropriate because the NC reactions are of the n, gamma type, rather than fission. Most of the energy released in such reactions is dissipated over relatively long distances. However we have re-examined the case of 157Gd, which has the highest thermal neutron capture cross section of all naturally occurring nuclides. In particular we addressed the possibility that conversion of some of the gamma energy, might result in the emission of low energy Auger electrons. Auger electron emission is associated with the disintegration of isotopes that decay by electron capture and/or internal conversion, resulting in intense, localised radiochemical. For example decay of DNA-associated 125I results in the induction of DNA double-strand (ds) breaks, and incorporation of 125I into DNA, or treatment with 125I-labelled DNA ligands, i3 cytotoxic. Our experiments have shown that irradiation of mixtures of Gd3+ and plasmid DNA with thermal neutrons results in the induction of DNA ds breaks. Inclusion of EDTA markedly reduces the damage, indicating the requirement that the GdNC event must be closely associated with DNA to induce a DNA ds break. The results clearly indicate a potential for 157Gd-labelled DNA ligands for NCT. We are synthesising a number of DNA ligands conjugated to macrocyclic chelators. In the meantime, control experiments involving irradiation of V79 cells with thermal neutrons in the presence of Gd-citrate, indicate that relatively high concentrations of non-DNA-bound Gd are required to increase cell kill.

Description

Physical copy held by ANSTO Library at DDC: 571.45/14.

Keywords

Gadolinium, Neutron capture therapy, Neoplasms, Cross sections, Alpha particles, Biological materials, Radiopharmaceuticals, Gadolinium 157, DNA, Ligands, Synthesis

Citation

Martin, R. F., Whittaker, A., Cunha, G. D., Haigh, A., Pardee, M., Allen, B. J., & Kelly, D. P. (1989). Gadolinium neutron capture. Presentation to the 12th AINSE Radiation Biology Conference, 22-24th September 1989, Lucas Heights, (pp. 25). Lucas Heights, New South Wales : AINSE.