Synthesis and biodistribution studies of two novel radioiodinated areno-annelated estra-1,3,5(10),16-tetraene-3-ols as promising estrogen receptor radioligands

Two novel radioiodinated areno-annelated estra-1,3,5(10),16-tetraenes, [I-125]2-iodo-l'-methoxybenzo[4',3':16,17]estra-1,3,5(10),16-tetraene-3-ol (2-[I-125]-MEBE) and [I-125]4-iodo-l'-methoxybenzo[4',3':16,17]estra-1,3,5(10),16-tetraene-3-ol, (4-[I-125]-MEBE) were synthesized for evaluation as potential ligands for the estrogen receptor. Radioiodination of l'-methoxybenzo[4',3: 16,17]estra-1,3,5(10),16-tetraene-3-ol at the A ring was accomplished by electrophilic aromatic substitution using [I-125] sodium iodide and chloramine-T as oxidant. After purification by reverse phase HPLC, the two radioisomers (2-[I-125]-MEBE and 4-[I-125]-MEBE) were obtained in a radiochemical yield of 42 and 48%, respectively, in a radiochemical purity of greater than 95% and a high specific activity. The effect of the site of radioiodination (C-2 VS C-4) on the biological behaviour of the molecules was evaluated through biodistribution studies in immature female Sprague-Dawley rats. Both 2-[I-125]-MEBE and 4-[(125)1]-MEBE are stable in vivo and are mainly excreted through the hepatobiliary pathway. Both localize in the uterus and ovaries via a receptor-mediated process, where the 2-[I-125]-MEBE isomer has the higher specific ER binding and uterus selectivity.