Studies on Ruthenium Nitroimidazoles Complexes as Radiosensitizers

Abstract

Local control of tumours by radiotherapy may fail due to the presence of hypoxic cells in tumours. Nitroimidazoles enchance killing of these resistant cells with ionizing radiation, presumably due to their electron affinity which permits electron abstraction from irradiated DNA to increase cell kill (1). However, dose-limiting side-effects have prevented the attainment of maximum sensitization by nitroimidazoles in the clinic. A desirable aim is to decrease the overall concentration of radiosensitizer (to decrease side-effects), while retaining a high drug concentration at the target of ionizing radiation, the DNA. The attachment of a radiosensitizer to metals that bind to DNA may serve this purpose (2). The successful chemotherapeutic drug, cisplatin and analogues have shown moderate radiosensitizing effects (3) possibly due to their DNA binding rather than by electron affinity. As a consequence of binding to DNA, the metal could act as a carrier of radiosensitizer to the target while maintaining its own radiosensitizing effect.