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.

Metal complex SERMs (selective oestrogen receptor modulators). The influence of different metal units on breast cancer cell antiproliferative effects

“…The biological evaluation in vitro as well as in vivo showed that both the Tc and Re chelates derived from tamoxifen had a very limited association with respect to the ER, making them practically unusable as tumour imaging reagents (RBA <0.009%). 30 With the aim of coupling tamoxifen to a boron neutron capture therapy (BNCT) agent, the boroxifen, with a nido carborane, was prepared, Chart 4. 31 This compound, however, has no affinity for the oestrogen receptor due to the absence of the hydrogen bonding phenol group.…”

Biocatalytic virus capsid as nanovehicle for enzymatic activation of Tamoxifen in tumor cells

“…Thus, the administered substances and their active metabolites accumulate in most normal tissues as well as in tumors in which their concentrations are significantly higher than in serum. . Nowadays, many studies using nanomaterials for oncological treatments focused precisely on drug delivery to specific tissues in the body to reduce the doses, minimize side effects and improve its function compared to conventional treatments .…”

Investigation of isomer formation upon coordination of bifunctional histidine analogues with 99mTc/Re(CO)3

“…The [TcvO] 3+ core forms complexes with square pyramidal geometry upon treatment with various tetradentate ligand sets. [2][3][4][5] However, the presence of an unprotected side adjacent to the oxo ligand left these complexes open to protonation, which could lead to decomposition. 6 The use of technetium in the +1 oxidation state was pioneered by Davison, Jones et al, 7 and was developed for use in radiopharmaceuticals by Alberto et al [8][9][10][11][12] These octahedral Re/Tc tricarbonyl complexes, when coordinated with a tridentate chelator, are completely protected against ligand attack.…”