title: The Z-isomer of 11 beta-methoxy-17 alpha-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer.
abstract: The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17 alpha-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[123I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[123I]MIVE. The uterus- and tumour-to-nontarget tissue (far, muscle) uptake ratios were also highest for Z-[123I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[123I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[123I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer.
authors.affiliation: Department of Nuclear Medicine, University of Amsterdam, The Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Rijks
authors.forename: G J
authors.initials: GJ
authors.lastname: Boer
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: K
authors.initials: K
authors.lastname: de Bruin
authors.forename: A G
authors.initials: AG
authors.lastname: Janssen
authors.forename: E A
authors.initials: EA
authors.lastname: van Royen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol; C042716:17 alpha-iodovinyl-11 beta-methoxyestradiol