Evaluation of Nitroheterocyclic Radiosensitizers Using Spheroids

Abstract

Publisher Summary This chapter focuses on the studies regarding in vitro testing of sensitizers largely using multicell spheroids, and presents the optimistic and pessimistic views as to the future of hypoxic cell sensitizers in the clinical setting. Some nitroheterocycles show promise for enhancing the response of selected tumors to radiation. Use of the drugs in humans is predicated on the belief that the presence of hypoxic cells within some tumors limits the success of conventional radiotherapy; however, in many tumors, conclusive evidence supporting this prejudice is lacking. The development of new drugs may be self-limiting as nitroheterocycles that are more effective as sensitizers are generally more reactive at a biochemical level. The effects of the nitroheterocycles can be observed under controlled and quantifiable conditions, and the roles of growth inhibition, cytotoxicity, and radiosensitization can be separated. The correlations between chemical and biological activities of nitroheterocycles suggest that at least with compounds that are effective as sensitizers only through the property of nitro-group reactivity, sensitization and toxicity are likely to be inseparable. As with most predictions, this may or may not be accurate. Combinations of radiation and hypoxic cell sensitizers with other modalities such as hyperthermia and selected chemotherapeutic agents such as alkylating agents, and even radioprotectors may improve the therapeutic ratio.