Development of Novel Technetium-99m-Labeled Steroids as Estrogen-Responsive Breast Cancer Imaging Agents

Abstract

Abstract : The overall objective of this project is the development of new Tc-99m-labeled steroids that can be used for single photon imaging of estrogen responsive breast cancer. The technical aims for the initial period involved preparation and characterization of an initial series of functionalized estradiols, their evaluation as ligands for the estrogen receptor, and initial conversion to the corresponding rhenium tricarbonyl derivatives. We have successfully undertaken these specific aims. We have prepared several pyridyl and histidinyl containing estradiols using Stille and Suzuki coupling methods, and characterized them using NMR and elemental analysis or MS. The appropriate biological assays- ER-alpha and ER-beta ligand binding domain competitive binding assays, and induction of alkaline phosphatase in Ishikawa cells- have been established and applied to several compounds in the initial series. Experiments evaluating the coordination of rhenium carbonyl reagents with pyridyl, bipyridyl and histinyl species are in progress. Aims for the second year include completion of these initial goals and evaluation in vitro and in vivo of the rhenium tricarbonyl-estrogen complexes.