Fluorine-18 Labeled Fluorofuranylnorprogesterone ([(18)F]FFNP) and Dihydrotestosterone ([(18)F]FDHT) Prepared by “Fluorination on Sep-Pak” Method

To further explore the scope of our recently developed “fluorination on Sep-Pak” method, we prepared two well-known positron emission tomography (PET) tracers 21-[(18)F]fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione furanyl norprogesterone ([(18)F]FFNP) and 16β-[(18)F]fluoro-5α-dihydrotestosterone ([(18)F]FDHT). Following the “fluorination on Sep-Pak” method, over 70% elution efficiency was observed with 3 mg of triflate precursor of [(18)F]FFNP. The overall yield of [(18)F]FFNP was 64–72% (decay corrected) in 40 min synthesis time with a molar activity of 37–81 GBq/µmol (1000–2200 Ci/mmol). Slightly lower elution efficiency (~55%) was observed with the triflate precursor of [(18)F]FDHT. Fluorine-18 labeling, reduction, and deprotection to prepare [(18)F]FDHT were performed on Sep-Pak cartridges (PS-HCO(3) and Sep-Pak plus C-18). The overall yield of [(18)F]FDHT was 25–32% (decay corrected) in 70 min. The molar activity determined by using mass spectrometry was 63–148 GBq/µmol (1700–4000 Ci/mmol). Applying this quantitative measure of molar activity to in vitro assays [(18)F]FDHT exhibited high-affinity binding to androgen receptors (K(d)~2.5 nM) providing biological validation of this method.