Single Isomer Technetium-99m Tamoxifen Conjugates

• Published in: Bioconjugate chemistry 2000-03, Vol.11 (2), p.175-181
• Main Authors: Hunter, Duncan H, Luyt, Leonard G
• Format: Article
• Language: English
• Subjects: Animals; Biological Assay; Chelating Agents - chemistry; Female; Isomerism; Mice; Mice, Inbred C3H; Molecular Structure; Organotechnetium Compounds - chemistry; Organotechnetium Compounds - metabolism; Organotechnetium Compounds - pharmacokinetics; Radioligand Assay; Radiopharmaceuticals; Receptors, Estrogen - metabolism; Rhenium - chemistry; Sheep; Tamoxifen - analogs & derivatives; Tamoxifen - chemistry; Tamoxifen - pharmacokinetics; Tissue Distribution; Uterus - chemistry
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc990110z

To produce an imaging agent for breast cancer using a technetium-99m-labeled agent specific for estrogen receptors, an N2S2 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.