THE STEREOISOMERS OF 17-ALPHA-[I-123]IODOVINYLOESTRADIOL AND ITS 11-BETA-METHOXY DERIVATIVE EVALUATED FOR THEIR ESTROGEN-RECEPTOR BINDING IN HUMAN MCF-7 CELLS AND RAT UTERUS, AND THEIR DISTRIBUTION IN IMMATURERATS

We studied the potential of both stereoisomers of 17 alpha-[I-123]iodo vinyloestradiol (E- and Z-[I-123]IVE) and of 11 beta-methoxy-17 alpha- [I-123]iodovinyloestradiol (E- and Z-[I-123]MIVE) as suitable radiolig ands for the imaging of oestrogen receptor(ER)-positive human breast t umours, The 17 alpha-[I-123]iodovinyloestradiols were prepared stereos pecifically by oxidative radio-iododestannylation of the corresponding 17 alpha-tri-n-butylstannylvinyloestradiol precursors. Competitive bi nding studies were performed in order to determine the relative bindin g affinity (RBA) of the unlabelled 17 alpha-iodovinyloestradiols for t he ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their I-123-labelled analogues we re studied in immature female rats, All four 17 alpha-iodovinyloestrad iols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreas ing potency: RBA of DES > Z-IVE > Z-MIVE > E-MIVE greater than or equa l to E-IVE. Neither of these 17 alpha-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasm a. The biodistribution studies showed ER-mediated uptake in the uterus , ovaries and pituitary, that of E- and Z-[I-123]MIVE being higher tha n that of E- and Z-[I-123]IVE, High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), we re exhibited by both isomers of [I-123]MIVE. The uterus-to-blood uptak e ratio was higher for E-[I-123]MIVE. However, the uterus-to-fat uptak e ratio appeared to be higher for the Z-isomer of [I-123]MIVE, especia lly at 24 h after injection, Metabolic properties and temperature effe cts, which play a more important role in vivo, probably cause the disc repancies seen between in vitro and in vivo binding results. On the ba sis of their in vitro binding properties and in vivo distribution char acteristics we conclude that E- and Z-[I-123]MIVE could be suitable ra dioligands for the diagnostic imaging of ER in human breast cancer, Th erefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted.