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Pharmacological characterization of 18 F‐labeled vorozole analogs
Author(s) -
Hall Håkan,
Takahashi Kayo,
Erlandsson Maria,
Estrada Sergio,
Razifar Pasha,
Bergström Elisabeth,
Långström Bengt
Publication year - 2012
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2982
Subject(s) - in vivo , chemistry , aromatase , in vitro , ex vivo , endocrinology , medicine , biochemistry , biology , microbiology and biotechnology , cancer , breast cancer
Two 18 F‐labeled analogs of vorozole ([ 18 F]FVOZ and [ 18 F]FVOO) have been developed as potential tools for the in vivo characterization of aromatase. The pharmacological properties of these radioligands were evaluated using in vitro binding and in vivo distribution studies in the rat and primate. Saturation binding studies using rat ovary gave K D and B max values of 0.21 ± 0.1 nM and 210 ± 20 fmol/mg, respectively, for [ 18 F]FVOZ, and 7.6 ± 1 nM and 293 ± 12 fmol/mg, respectively, for [ 18 F]FVOO. Organ distribution studies in rats showed the highest accumulation in the adrenal glands, with standardized uptake values (SUVs) of 15 to 20, followed by ovaries and liver with SUVs of approximately 5. Ex vivo and in vitro autoradiography of the rat brain showed specific binding of both [ 18 F]FVOZ and [ 18 F]FVOO mainly in the amygdala. Positron emission tomography (PET) studies were performed in the Rhesus monkey, and these showed displaceable binding in the amygdala and the hypothalamus preoptic area. The PET images were also analyzed using masked volume‐wise principal component analysis. These studies suggest that [ 18 F]FVOZ might be a suitable tracer for the study of aromatase in vitro and in vivo, and could be an alternative to [ 11 C]vorozole in human PET studies. Copyright © 2012 John Wiley & Sons, Ltd.