Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation

A novel I-131-radiolabeled probe with aromatic boronate motif (I-131-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 I-131 to afford I-131-EIPBA. Meanwhile, I-131-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 I-131-EIPBA. I-131-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 I-131-EIPBA for PR was determined by cell binding assay. The internalization ratio of I-131-EIPBA was remarkably higher than that of I-131-EIPB in PR-positive MCF-7 cells. Furthermore, the enhanced nucleus uptake of I-131-EIPBA (0.59 +/- 0.02%) was found to be significantly higher than that of I-131-EIPB (0.13 +/- 0.01%) in MCF-7 cells. A novel I-131-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.