Pharmacological characterization of 18F-labeled vorozole analogues.
(English)Manuscript (Other academic)
Two 18F-labeled analogues of vorozole ([18F]FVOZ and [18F]FVOO) have been developed as potential tools for the in vivo characterization of aromatase. The purpose of the project was to evaluate the pharmacological properties of these radioligands using a combination of in vitro binding and in vivo distribution studies in the rat and primate. Saturation binding studies with the radioligands in homogenates of rat ovary gave KD and Bmax values of 0.21 ± 0.1 nM and 210 ± 20 fmol/mg, respectively, for [18F]FVOZ, and 7.6 ± 1 nM and 293 ± 12 fmol/mg, respectively, for [18F]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. The SUVs in the remaining organs were between 0.5 and 1.5. There was probably some defluorination of both radioligands, as the accumulation of radioactivity in bone increased with time. The regional distribution in the brain was studied using ex vivo and in vitro autoradiography. In the brain, specific binding of both [18F]FVOZ and [18F]FVOO were found mainly in the amygdala. PET studies were performed in the Rhesus monkey, and these showed displaceable binding in the amygdala and the preoptic area of the hypothalamus. These studies suggest that [18F]FVOZ might be to be a suitable tracer for the study of aromatase in vitro and in vivo, and could be an alternative to [11C]vorozole in human PET-studies.
aromatase, autoradiography, biodistribution, PET, rat brain, vorozole
Other Basic Medicine Medical and Health Sciences
Research subject Organic Chemistry; Medicine
IdentifiersURN: urn:nbn:se:uu:diva-88793OAI: oai:DiVA.org:uu-88793DiVA: diva2:159099