The development of estrogen and progestin radiopharmaceuticals for imaging breast cancer

The presence of receptors for estrogens and progestins in many breast tumors provides a means for imaging these tumors using positron emission tomography (PET) with appropriate fluorine-18 labeled estrogen and progestin radiopharmaceuticals. In this context, the estrogen analog 16 alpha-[18F]fluoroestradiol (FES) has already proven to be an effective imaging agent for estrogen receptor-positive tumors.

Clinical studies comparing FES images with those based on the metabolic probe 2-[18F]fluoro-2-deoxyglucose (FDG) in patients before and after tamoxifen hormone therapy are underway. Several fluorine-18 labeled progestins have been prepared, and efforts are underway to develop methods for labeling steroid receptor imaging agents with the widely available radionuclide technetium-99m, using both pendant and integrated approaches.

Breast tumor imaging with FES and FDG shows an interesting relationship between tumor metabolic response (assessed with FDG) and tumor estrogen receptor levels (assessed with FES). The fluorine-18 labeled progestins show excellent target tissue selective distribution in experimental animals and are ready for imaging studies in humans. The development of steroids labeled with technetium-99m poses special challenges because of the metallic nature of this radioisotope.