Synthesis and preliminary evaluation of a 18 F-labeled ethisterone derivative [18 F]EAEF for progesterone receptor targeting.

Abstract

To develop a novel progesterone receptor-targeting probe for positron emission tomography imaging, an ethisterone derivative [18 F]EAEF was designed and prepared in high decay-corrected radiochemical yield (30-35%) with good radiochemical purity (>98%). [18 F]EAEF is a lipophilic tracer (logP=0.53±0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [18 F]EAEF were found in uterus (5.73±1.83% ID/g) and ovary (4.05±0.73% ID/g) at 2hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50±0.17% ID/g). For positron emission tomography imaging, [18 F]EAEF showed high uptake in progesterone receptor-positive MCF-7 tumor (3.15±0.07% ID/g at 2hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7 with EAEF blocking (1.84±0.05% ID/g at 2hr p.i.) or in progesterone receptor-negative MDA-MB-231 tumor (1.80±0.03% ID/g at 2hr p.i.). Based on the good stability and specificity of [18 F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation.