TY - JOUR
T1 - Bromine-80m-labeled Estrogens
T2 - Auger Electron-emitting, Estrogen Receptor-directed Ligands with Potential for Therapy of Estrogen Receptor-positive Cancers
AU - DeSombre, Eugene R.
AU - Mease, Ronnie C.
AU - Hughes, Alun
AU - Harper, Paul V.
AU - DeJesus, Onofre T.
AU - Friedman, Arnold M.
PY - 1988
Y1 - 1988
N2 - To assess their possible use for estrogen receptor (ER)-directed radio therapy of estrogen receptor-containing cancers, two estrogens were synthesized with the Auger electron-emitting nuclide bromine-80m and administered to immature female rats. Both the triphenylethylene-based estrogen, |80mBr]-2-bromo-l,l-bis(4-hydroxyphenyl)phenylethylene (Br- BHPE) and the steroidal estrogen |80mBr|17a-bromovinylestradiol, showed substantial diethylstilbestrol-inhibitable localization only in the estrogen target tissues, the uterus, pituitary, ovaries, and vagina and, except for the liver and intestines, generally lower concentrations in all other tissues at both 0.5 and 2 h. The |80mBr|Br-BHPE (specific activity, 8700 Ci/mmol), was shown to bind specifically to the low salt extractable ER of the rat uterus. Comparing P.,i.V., and s.c. administration of |HBr|BlIIKthe i.p. route was found to be particularly advantageous to effect maximum, DES-inhibitable concentrations of radiobromine in the ER-rich target organs in the peritoneal cavity. When the tissue distribution of the CBr|Br-BIIPK was compared with that of sodium bromide- 80m, it was apparent that no substantial amounts of radiobromine were released from the bromoestrogen prior to its target tissue localization. The substantial concentration of these bromine-80m-labeled estrogens in ER-rich tissues, combined with previously reported evidence for the effective radiotoxicity of Auger electron-emitting nuclides within cell nuclei suggest a good potential for such ligands for therapy of ER positive cancers.
AB - To assess their possible use for estrogen receptor (ER)-directed radio therapy of estrogen receptor-containing cancers, two estrogens were synthesized with the Auger electron-emitting nuclide bromine-80m and administered to immature female rats. Both the triphenylethylene-based estrogen, |80mBr]-2-bromo-l,l-bis(4-hydroxyphenyl)phenylethylene (Br- BHPE) and the steroidal estrogen |80mBr|17a-bromovinylestradiol, showed substantial diethylstilbestrol-inhibitable localization only in the estrogen target tissues, the uterus, pituitary, ovaries, and vagina and, except for the liver and intestines, generally lower concentrations in all other tissues at both 0.5 and 2 h. The |80mBr|Br-BHPE (specific activity, 8700 Ci/mmol), was shown to bind specifically to the low salt extractable ER of the rat uterus. Comparing P.,i.V., and s.c. administration of |HBr|BlIIKthe i.p. route was found to be particularly advantageous to effect maximum, DES-inhibitable concentrations of radiobromine in the ER-rich target organs in the peritoneal cavity. When the tissue distribution of the CBr|Br-BIIPK was compared with that of sodium bromide- 80m, it was apparent that no substantial amounts of radiobromine were released from the bromoestrogen prior to its target tissue localization. The substantial concentration of these bromine-80m-labeled estrogens in ER-rich tissues, combined with previously reported evidence for the effective radiotoxicity of Auger electron-emitting nuclides within cell nuclei suggest a good potential for such ligands for therapy of ER positive cancers.
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M3 - Article
C2 - 3338083
AN - SCOPUS:0023901474
SN - 0008-5472
VL - 48
SP - 899
EP - 906
JO - Cancer Research
JF - Cancer Research
IS - 4
ER -