Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine substitution at the 16alpha-position of fulvestrant (faslodex; ICI 182,780)

Nuclear Medicine and Biology
Yann SeimbilleJohan E van Lier

Abstract

Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16alpha-[18F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ERalpha and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18F would have led to a product of low specific activity; instead we selected the 16alpha-position for 18F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [18F]fluoride at the 16-18F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the pr...Continue Reading

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Citations

Apr 4, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Rakesh Kumar
Jul 25, 2007·Physica Medica : PM : an International Journal Devoted to the Applications of Physics to Medicine and Biology : Official Journal of the Italian Association of Biomedical Physics (AIFB)·David A Mankoff
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