Synthesis, receptor binding and tissue distribution of 17 alpha-E[125I]iodovinyl-11 beta-ethyl-estradiol.
In this study we prepared and evaluated a derivative of estradiol with an ethyl group at the 11 beta-position and an E-iodovinyl group at the 17 alpha-position. This new ligand binds to the estrogen receptor with an affinity slightly less than estradiol (RBA = 43%) at 0 degree C but much greater (RBA = 890%) at 25 degrees C. The 125I-labeled derivative was obtained by radioiododestannylation of the tri-n-butylstannyl precursor in good radiochemical yield with a specific activity exceeding 1500 Ci/mmol. The tissue distribution in immature female rats was evaluated over a 48 h period to determine uterine uptake and selectivity. Peak uterine uptake at 2 h was 6% ID/g and was significantly greater than that of [3H]estradiol, 2.4% ID/g. Substantial uptake in the uterus was still present at 48 h (2.4% ID/g). Co-administration of estradiol reduced the uptake at 2 and 24 h by 85%. Uterus-to-plasma ratios increased with time, from about 25:1 at 2 h to nearly 90:1 at 48 h. The affinity, ease of radiosynthesis and tissue distribution of the 17 alpha-E-[125I]iodovinyl-11 beta-ethyl-estradiol suggest that further evaluation of this agent as an imaging agent for estrogen-receptor-positive breast cancer is warranted.
Hanson
R N
RN
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Ghoshal
M
M
Murphy
F G
FG
Rosenthal
C
C
Gibson
R E
RE
Ferriera
N
N
Sood
V
V
Ruch
J
J
D000818:Animals; D001667:Binding, Competitive; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D012756:Sheep; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; C081032:17-iodovinyl-11-ethylestradiol; D004958:Estradiol