Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via...

A novel ¹³¹ I-radiolabeled probe with aromatic boronate motif (¹³¹ I-EIPBA) was designed to target progesterone receptor (PR)-positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phenylboronic acid via click reaction and radiolabeled with ¹³¹ I to afford ¹³¹ I-EIPBA. Meanwhile, ¹³¹ I-EIPB without boronate was prepared as control agent. After determination of the lipophilicity and stability of these tracers, in vitro cell uptake studies and in vivo biodistribution in rats were performed to verify the enhanced nucleus uptake and PR targeting ability of ¹³¹ I-EIPBA. ¹³¹ I-EIPBA was obtained with moderate radiochemical yield (40.35 ± 3.52%) and high radiochemical purity (>98%). As expected, the high binding affinity (39.58 nM) of ¹³¹ I-EIPBA for PR was determined by cell binding assay. The internalization ratio of ¹³¹ I-EIPBA was remarkably higher than that of ¹³¹ I-EIPB in PR-positive MCF-7 cells. Furthermore, the enhanced nucleus uptake of ¹³¹ I-EIPBA (0.59 ± 0.02%) was found to be significantly higher than that of ¹³¹ I-EIPB (0.13 ± 0.01%) in MCF-7 cells. A novel ¹³¹ I-EIPBA compound was developed for PR targeting with improved cellular nucleus uptake. Furthermore, the introduction of aromatic boronate motif provides a worthwhile strategy for enhancing the nuclear receptor targeting of tracers.