PET imaging of breast cancer with fluorine-18 radiolabeled estrogens and progestins.

Through the use of fluorine-18 radiolabeled estrogen receptor ligands and Positron Emission Tomography (PET), imaging of estrogen receptor-positive (ER+) breast lesions has been accomplished. Targeting the estrogen and progesterone receptors found in receptor-positive breast cancer provides a means of diagnosing the disease non-invasively. The structure-activity relationship of evaluated fluorine-18 ligands are summarized and design considerations for construction of novel target ligands discussed. The role of the serum protein sex hormone-binding globulin (SHBG) in transport and metabolism of estrogens is related to target tissue uptake. A historical review of fluorine-18 radiolabeled estrogens includes the clinical study of 16 alpha-[18F]fluoroestradiol-17 beta (18FES) for imaging ER+ breast lesions. The success of 18FES in the clinical setting has shown the significance of PET in imaging primary and metastatic breast cancer by allowing for assessment of tumor response to tamoxifen therapy after as little as 7 days of treatment. Advantages of visualizing the tumor through targeting the progesterone receptor (PR) include PET imaging to follow the progress of tamoxifen therapy while the estrogen receptors are blocked. Clinical studies with the PR ligand 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (18FENP) were not successful due to high hepatic uptake and poor correlation of tumor uptake with receptor content. Second generation PR ligands with decreased non-specific binding are predicted to be effective imaging agents for human PR+ breast cancer from studies in the immature rat and are ready for clinical evaluation.