Sex-dependent organ distribution of radiopharmaceuticals: effect of hormones on localization of acetyl-103Ru-ruthenocene.
This paper demonstrates modification of organ distribution of a radiopharmaceutical, acetyl-103Ru-ruthenocene, by competing drugs. This radiopharmaceutical concentrates in kidneys of male Wistar rats 15-fold higher than in females of the same strain and age. This concentration in the male is age-dependent. Moreover, the retention of that radiopharmaceutical in male rats' kidneys is markedly reduced by pre-treatment of the rats with estradiol, and this effect is dose-dependent. Estradiol is competetively inhibiting the retention of acetyl-ruthenocene by the kidneys, the same effect also being obtained by tamoxifen, an anti-estrogen used clinically for regression of mammary carcinoma. Blocking the retention of acetyl-ruthenocene was also obtained by testosterone and cyproterone-acetate, as well as by ovariectomy, but the block after castration was partially compensated with time. Blood clearance of acetyl-ruthenocene is biphasic, with a first t 1/2 of about 12 h, and a second t 1/2 of about 48 h. The retention of the label is sex-specific also in mice, but only the female mice show a high adrenal affinity and significant changes in its organ distribution. These effects may be due to competition of acetyl-ruthenocene for steroid receptors, or due to its activation of enzymes that are responsible for its transformation into a bindable moiety.
Shani
J
J
Livshitz
T
T
Wenzel
M
M
D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D012428:Ruthenium / Q000378:metabolism*; D012737:Sex Factors; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
D003272:Contraceptive Agents, Male; D012739:Gonadal Steroid Hormones; D009942:Organometallic Compounds; D011868:Radioisotopes; D013629:Tamoxifen; C016199:acetylruthenocene; D013739:Testosterone; D017373:Cyproterone Acetate; D004958:Estradiol; D012428:Ruthenium; D003534:Cyproterone