title: Single isomer technetium-99m tamoxifen conjugates.
abstract: To produce an imaging agent for breast cancer using a technetium-99m-labeled agent specific for estrogen receptors, an N(2)S(2) bifunctional chelator was conjugated to Z- and E-aminotamoxifens through an amide linker. These bioconjugates have been chelated with both technetium-99m and rhenium. For the Z-isomer, chelation with rhenium in the presence of sodium acetate yields a mixture of two isomers, anti and syn, in a 1:1 ratio and in the presence of hydroxide results in only the anti isomer. Both the Z- and E-tamoxifen conjugates have been chelated with technetium-99m at the tracer level yielding a single isomer product, which is assigned as anti based on chromatographic comparison to the rhenium complexes. Radiochemical yields were consistently greater than 80%, with Sep-Pak column purification yielding a final product with >99% radiochemical purity and no residual starting material. Both in vitro and in vivo biological evaluation of the tamoxifen chelates indicated very limited estrogen receptor binding.
authors.affiliation: Department of Chemistry, University of Western Ontario, London, Ontario, Canada N6A 5B7. dhunter@julian.uwo.ca
authors.forename: D H
authors.initials: DH
authors.lastname: Hunter
authors.forename: L G
authors.initials: LG
authors.lastname: Luyt
mesh_terms: D000818:Animals; D001681:Biological Assay; D002614:Chelating Agents / Q000737:chemistry; D005260:Female; D007536:Isomerism; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen / Q000378:metabolism; D012211:Rhenium / Q000737:chemistry; D012756:Sheep; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014599:Uterus / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D013629:Tamoxifen; D012211:Rhenium