Interactions of 16 alpha-[F-18]-fluoroestradiol (FES) with sex steroid binding protein (SBP)

Fluorine-18 16 alpha-Fluoroestradiol ([F-18]-FES) is a positron-emitting tr acer for the estrogen receptor that is used for positron emission tomograph y (PET) studies of tumor tissues rich in the estrogen receptor. The role of the sex steroid binding protein (SBP or SHBG) in the transport of the [F-1 8]-FES to the estrogen-receptor-rich tissue in breast cancer patients in vi vo was investigated. To determine the extent to which [F-18]-FES is bound t o SEP in the blood, Re performed a series of studies using blood samples ob tained from patients undergoing [F-18]-FES PET scans. The binding of [F-18] -FES to the SEP was measured using a simple protein precipitation assay. Th e binding of [F-18]-FES metabolites to SBP was also measured. These measure ments showed that the tracer was distributed between albumin and SBP, and t he binding capacity of SEP was sufficient to ensure that the protein was no t saturated when the tracer was fully mixed with the plasma; however, local saturation of SBP may occur when [F-18]-FES is administered intravenously. Typically about 45% of [F-18]-FES in circulating plasma was bound to SEP, but this fraction was dependent on the concentration of SEP in plasma. The transfer of the tracer between the two proteins was rapid, complete in less than 20 s at 0 degrees C, suggesting that the equilibrium was maintained u nder most circumstances and that local saturation resolved quickly when blo od from the injection site entered the central circulation. These data sugg est that SEP binding of [F-18] FES is significant and will affect the input function of the tracer for any model that is used for the quantitative eva luation of [F-18]-FES uptake in PET studies. Estimates of equilibrium bindi ng in blood samples are sufficient to characterize [F-18]-FES binding to SE P in the circulation. (C) 2000 Elsevier Science Inc. All rights reserved.