Biological activity of [ 127I] and [ 125I] estradiol analogs in vitro and in vivo

Abstract

In order to develop a means by which the receptor status of breast cancers could be studied in vivo. 127I and 125I analogs of estrogens were synthesized and their abilities to bind to uterine receptors, to translocate these receptors to the nucleus, and to bind in vivo to mammary tumors in rats were studied. 6-[ 127I]-Iodoestra-1,3,5(10),6-tetraene-3,17β-diol ( 2a), 16β[ 127I]-iodoestra-1,3,5(10)-triene-3,17β-diol ( 1) and 16α[ 127I]-iodoestra-1,3,5(10)-triene-3,17β-diol ( 3a) were capable of binding to the 8S cytosol receptor, translocating the cytosol receptor to the nucleus, in vitro, and increasing uterine weight in vivo. 16α-[ 125I]-Iodoestradiol ( 3b) was found to bind to high affinity 8S cytosol receptors but 6-[ 125I]-iodoestratetraene ( 2b) appeared to bind only non-specifically to macromolecules sedimenting in the 4S region. When these compounds ( 2b) and ( 3b) labeled with 125I, were administered to rats with DMBA-induced mammary tumors, the radioactivity as determined by imaging techniques was noted primarily in the liver and intestines. However, some rat tumors appeared to concentrate compound ( 2b). In at least one such tumor, the iodinated estrogen ( 2b) was bound non-specifically to 4S proteins.