Synthesis and biodistribution of fluorine-18-labeled fluorocyclofenils for imaging the estrogen receptor

Abstract 

C4-[¹⁸F]Fluorocyclofenil ([¹⁸F]FCF, 6) and C3-[¹⁸F]fluoroethylcyclofenil ([¹⁸F]FECF, 9), two high-affinity nonsteroidal estrogens, were prepared and investigated as potential agents for imaging estrogen receptors (ERs) in breast tumors. Both of these compounds could be prepared conveniently from alkyl methanesulfonate precursors (5,8) by fluoride displacement reactions, and they were obtained in high radiochemical purity and radiochemical yields, with effective specific activities sufficient for in vivo biodistribution studies. While the biodistribution of [¹⁸F]FCF (6) in immature female rats showed no selective target tissue uptake, the biodistribution of [¹⁸F]FECF (9) showed selective uptake by the uterus, but this uptake could not be blocked by excess estradiol. The poor in vivo biodistribution of these otherwise high-affinity ligands arouses curiosity, and together with recent results on the biodistribution of other nonsteroidal ligands suggests that factors other than receptor binding affinity are important for in vivo imaging of estrogen target tissues and ER-positive breast tumors.

Keywords: Cyclofenil, Estrogen receptor, Estrogen receptor imaging, Fluorine-18