Synthesis of ¹⁰B- and ¹⁵⁷Gd-Labelled DNA Ligands for Neutron Capture Therapy

Abstract

Experiments with plasmid DNA have demonstrated that neutron capture by DNA-associated ¹⁵⁷Gd induces DNA double-strand breaks, presumably mediated by the Auger electron emission accompanying internal conversion, which in turn is associated with the n, gamma reaction¹. Those experiments involved use of GdCl₃ in a low ionic strength buffer, which allowed ionic association of the Gd³⁺ with phosphate groups on the DNA. Dissociation of the Gd³⁺/DNA complex by inclusion of EDTA markedly decreased the DNA damage induced by thermal neutron irradiation, reflecting the limited range of Auger electrons. Given the established² radiobiological toxiCity of DNA-associated decay of Auger-emitting isotopes such as ¹²⁵I and the high thermal neutron capture cross-section of ¹⁵⁷Gd, there is obvious potential to exploit ¹⁵⁷GdNC for NCT. However, a stable Gd-DNA association is a clear prerequisite, and we have therefore undertaken the synthesis of Gd-labelled DNA ligands.