SYNTHESIS, ESTROGEN-RECEPTOR BINDING, AND TISSUE DISTRIBUTION OF A NEW IODOVINYLESTRADIOL DERIVATIVE TRATO-19-NORPREGNA-1,3,5(10),20-TETRAENE-3,17-DIOL (E-[I-123]NIVE)

We have synthesized and evaluated E-11 beta-nitrato-17 alpha-iodovinyl estradiol (E-NIVE; E-3c) and its I-123-labelled form, as a new potenti al radioligand for imaging of estrogen receptor (ER)positive human bre ast tumors. E-[I-123]NIVE was prepared by stereospecific iododestannyl ation of the E-tri-n-butylstannylvinyl precursor (E-2c), obtained from reaction of 11 beta-nitrato estrone (8) with E-tributylstannylvinylli thium. In competitive binding studies, E-NIVE proved to have high bind ing affinity for both the rat and the human ER (K-i 280-730 pM), witho ut significant binding to human sex hormone binding globulin. Distribu tion studies in normal and mammary tumor bearing rats showed specific ER mediated uptake of E-[I-123]NIVE in the estrogen target tissues, i. e., uterus, ovaries, pituitary, and hypothalamus, but not in the mamma ry tumors. Selective retention in these target tissues, including tumo r tissue, resulted in significant increases over time for the target t issue-to-muscle uptake ratios, but not for the target tissue-to-fat up take ratios. The tumor-to fat uptake ratio even appeared constantly be low 1. In the primary estrogen target tissues, E-[I-123]NIVE displayed high specific ER-mediated uptake and retention, which resulted in mod erate target to-nontarget tissue uptake ratios. In contrast, in tumor tissue, E-[I-123]NIVE uptake appeared to be rather low and not ER-spec ific, As a consequence, E-[I-123]NIVE appears to be a less favorable r adioligand for ER imaging in breast cancer than the previously studied stereoisomers of 11 beta-methoxy-17 alpha-[I-123]iodovinylestradio (E - and Z-[I-123]MIVE; [I-123]E- and [I-123]Z-3b). (C) 1998 Elsevier Sci ence Inc.