THE Z-ISOMER OF 11-BETA-METHOXY-17-ALPHA-[I-123]IODOVINYLESTRADIOL ISA PROMISING RADIOLIGAND FOR ESTROGEN-RECEPTOR IMAGING IN HUMAN BREAST-CANCER

The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[I-123 ]iodovinylestradiol (E- and Z-[I-123]MIVE) as suitable radioligands fo r imaging of estrogen receptor(ER)-positive human breast tumours was s tudied. The 17 alpha-[I-123]iodovinylestradiol derivatives were prepar ed stereospecifically by oxidative radioiododestannylation of the corr esponding 17 alpha-tri-n-butylstannylvinylestradiol precursors. Both i somers of MIVE showed high in vitro affinity for dimethylbenzanthracen e-induced rat and fresh human mammary tumour ER, that of Z-MIVE howeve r being manyfold higher than that of E-MIVE. In vivo distribution stud ies with E- and Z-[I-123]MIVE in normal and tumor-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[I-123]MIVE . The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake rati os were also highest for Z-[I-123]MIVE. Additionally, planar whole bod y imaging of two breast cancer patients 1-2 h after injection of Z[I-1 23]MIVE showed increased focal uptake at known tumor sites. Therefore, we conclude that Z-[I-123]MIVE is a promising radioligand for the dia gnostic imaging of ER in human breast cancer. Copyright (C) 1997 Elsev ier Science Inc.