Synthesis, purification and stability of no carrier added radioiodinated 1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene (IBHPE), a prototype triphenylethylene estrogen-receptor binding radiopharmaceutical.
A triphenylethylene compound [1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; IBHPE] has been labeled by halodestannylation with 123I at a specific radioactivity of 13,200 Ci/mmol (by in vitro receptor assay) after HPLC purification. The corresponding 80mBr-labeled compound (BrBHPE), which has a 3-fold higher affinity for the estrogen receptor, was previously prepared and examined as a potential therapeutic radiopharmaceutical exploiting Auger electron toxicity. Stability of IBHPE was a concern because free iodide was generated when HPLC solvents were removed with a stream of nitrogen in a glass vial; however, decomposition was minimal when polypropylene vials were used, and ethanol solutions of [123I]IBHPE were stable for several days at 0-4 degrees C. Tissue distribution studies of IBHPE after intraperitoneal injection to mature female rats showed highest estradiol-inhibitable uptake in the peritoneal estrogen-receptor rich tissues (uterus, ovaries and vagina) at 30 min. Specific uptake (percent dose per gram) in the pituitary, and peritoneal target tissue-to-blood ratios were greater at 2 h than 30 min. In immature female rats, uterus-to-blood ratios of greater than 50, progressively lowered by increasing diethylstilbestrol levels, were obtained. These data demonstrate good binding of IBHPE to the estrogen receptor in vivo, in spite of extensive non specific binding in in vitro estrogen receptor assays. Most of the label in the uterus at 1 h after injection was still unchanged IBHPE. Our results suggest that IBHPE or related 123I-labeled iodovinyl triphenylethylenes could have diagnostic or therapeutic radiopharmaceutical utility.
Gatley
S J
SJ
Department of Radiology, University of Chicago, IL 60637.
Desombre
E R
ER
Mease
R C
RC
Seevers
R E
RE
Hughes
A
A
Li
J
J
Pan
M L
ML
D000375:Aging / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004965:Estrogen Antagonists / Q000378:metabolism*; D005260:Female; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013267:Stilbenes / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism*; D014018:Tissue Distribution; D014461:Ultracentrifugation; D014599:Uterus / Q000378:metabolism
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013267:Stilbenes; C072916:1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; C037749:triphenylethylene