Preparation of Meta -Carboranylpropyl-2-Nitroimidazole Derivatives for Application to BNCT

Abstract

Many types of tumor localizing boronated compounds have been studied for application to boron neutron capture therapy (BNCT) of cancer (1-4). However, compounds which are designed to localize in hypoxic regions of tumors (5) have not been studied. This is understandable as the focus of much of the previous research in this area has been directed towards use of thermal or epithermal neutron beams to treat the cancer, where the radiation dose from the heavy particles produced by neutron capture (He-4 & Li-7) must be lethal to all cancer cells for efficacious therapy. In contrast to this, our research focus has been to evaluate augmentation (boost) of the tumor dose obtained from a fast neutron beam (which also contains epithermal neutrons) when boron rich compounds are administered. Importantly, in an application that is directed at augmentation of fast neutron therapy (FNT) it is not necessary that all tumor cells contain boron-10 to obtain an efficacious therapy. Indeed, application of agents that are preferentially retained in hypoxic tissues in a combination therapy involving FNT and BNCT seems ideal as it targets high LET particles to a region of the cancer that is particularly resistant to radiation damage (6).