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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
1994-2-4
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pubmed:abstractText |
The effect of 2- and 4-fluoro substitution on the estrogen receptor-mediated tissue localization of radioiodinated 16 alpha-iodoestradiol (16 alpha-IE2) and its 11 beta-methoxy analogue (11 beta-OMe-16 alpha-IE2) was evaluated. Electrophilic substitution of estrone or 11 beta-methoxyestrone with N-fluoropyridinium salt gave the 2- and 4-fluoro derivatives which were subsequently converted to the 3,17 beta-enol diacetate and brominated to yield exclusively the 16 alpha-bromo analogues. Epimerization gave the corresponding 16 beta-bromoestrones which were reduced to the 17 beta-hydroxy derivatives. Halogen exchange with NaI or Na[125I]I provided the A-ring fluorinated 16 alpha-iodoestradiols. The 4-F analogue exhibited higher affinity for estrogen receptors than the corresponding 2-F analogue, and these differences were more pronounced at higher incubation temperatures. Biodistribution studies in immature female rats showed that 4-fluoro substitution had only a moderate effect on receptor-mediated tissue uptake of the parent molecules whereas 2-fluoro substitution resulted in strongly diminished tissue specificity. The lower target selectivity of the 2-F, compared to the 4-F, analogue correlates to some extent with their different receptor binding properties; however, the rate of catabolism may also be involved. Differences in blood clearance further accentuated the localization properties to yield particularly high uterus to blood ratios in the case of the 4-F-11 beta-OMe-16 alpha-IE2, suggesting the potential of the analog labeled with 123I as a radiopharmaceutical for receptor imaging in nuclear medicine. The isopotential maps of the fluorinated steroids, obtained via semiempirical computer modeling on the molecular structures, show striking differences between the 4-F and 2-F derivatives reflecting their varying biological properties.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/16 alpha-iodoestradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrone,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4255-63
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8277508-Animals,
pubmed-meshheading:8277508-Computer Simulation,
pubmed-meshheading:8277508-Estradiol,
pubmed-meshheading:8277508-Estrone,
pubmed-meshheading:8277508-Female,
pubmed-meshheading:8277508-Fluorine,
pubmed-meshheading:8277508-Iodine Radioisotopes,
pubmed-meshheading:8277508-Models, Molecular,
pubmed-meshheading:8277508-Molecular Structure,
pubmed-meshheading:8277508-Rats,
pubmed-meshheading:8277508-Receptors, Estrogen,
pubmed-meshheading:8277508-Structure-Activity Relationship,
pubmed-meshheading:8277508-Tissue Distribution,
pubmed-meshheading:8277508-Uterus
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pubmed:year |
1993
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pubmed:articleTitle |
2- and 4-fluorinated 16 alpha(-)[125I]iodoestradiol derivatives: synthesis and effect on estrogen receptor binding and receptor-mediated target tissue uptake.
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pubmed:affiliation |
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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