Figure 6. [18F]-FES

Intracellular receptors are a separate category of imaging agents that must both target a relevant binding partner and cross the cell membrane. The estrogen receptor is an intracellular receptor that is used to diagnose and stage breast cancers. Several PET imaging agents have been developed preclinically to evaluate the expression of these nuclear intracellular receptors such as 18F-fluoroestradiol.

FES has binding characteristics similar to estradiol for both  the  Estrogen Receptors and  the  transport  protein,  SHBG (45% of 18F FES in circulating plasma is  bound  to  SHBG,  and  much  of  the  reminder  is  weakly bound to albumin)

Like other steroids, FES is highly extracted by the liver and, once injected is rapidly taken up and metabolized. As a result, early blood clearance  is  rapid,  reaching  a  plateau  20-30  minutes  after injection. By 20 minutes, only 20% of the circulating radio-activity is in the form of non-metabolized FES. Metabolite excretion into the urine, mostly in the form of the glucuronide conjungates, occurs at a rate comparable with release from the liver.

There is a pattern of enterohepatic circulation, where metabolites excreted into the bile are efficiently reabsorbed  in  the  small  intestine,  with  little  radioactivity reaching the large intestine.  Because early FES clearance is rapidand metabolite background is nearly constant, imaging starting at 30 minutes after injection can provide good visualization  of  estrogen  containing  tissues,  even  in  sites  close  to blood pool structures.

Estrogen receptor kinetics: Estrogen must exist in the free form separated from its carrier protein (sex-steroid-binding globulin [SBG]) prior to diffusion intro the cell.
The strogen receptor undergoes a temperature-dependent conformational change to the 5.4S form prior to nuclear transport.
After interacting with the euchromatin, the receptor complex is probably recirculated.


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