Measurement of Boron Stable Isotopes for Cancer Therapy

Development of novel boronated compounds and use of epithermal neutrons has now generated much interest in 10B-boron capture neutron therapy of different tumors. However, no suitable methods exist that allow investigation of their pharmacokinetics in human subjects or in vivo measurement of the ratio of intracellu- lar/extracellular 10B at the time of irradiation. A new approach based on the use of stable isotopes of B is proposed for these purposes. During Phase I, the analytical chemistry of the method focusing on accurate measurement of stable isotopes 10B and 11B in fluids and tissues from humans and animals will be developed. Using this method, pharmacokinetics of selected boronated compounds will be investigated in a laboratory rat during Phase II. A new method based on the concept of in vivo isotope dilution coupled with the measurement of bromine space will be developed which will permit in vivo measurement of the ratio intracellular/extracellular 10B. The accuracy of this method will be tested against methods based on chemical analysis of carcass. During Phase III, the aggregate of this methodology will be employed to investigate pharmacokinetics of boronated drugs that are candidates for human use and to develop 10B-administration protocols for optimizing the ratio of intracellular/extracellular 10B at the time of irradiation. Since major advances are being made in development of promising boronated drugs, both private sector and public agencies will become active in development, marketing, and research related to this therapeutic mode. Thus, significant need will be generated for studies requiring accurate measurement of B in various tissues and fluids and in the use of the stable isotope methodology developed in the research. We expect to be able to act as an international center for collaborative investigations based on our methods.