Design, synthesis, and biochemical evaluation of three types of hexestrol-based probes for estrogen receptor: Fluorine-18 radiopharmaceuticals, bivalent ligands and diazirine photoaffinity reagents

The estrogen receptor (ER) has become a major focus of biological and clinical investigation in diagnostic and therapeutic drug design for human breast carcinoma. Molecular probes, such as fluorine-18 radiopharmaceuticals, bivalent ligands, and affinity labels, provide information toward a better understanding of ER localization, structure, and function. We have prepared two fluorinated analogs of 2-oxohexestrol as potential diagnostic imaging agents for ER-responsive human breast tumors. These ligands were prepared in fluorine-18 labeled form with high specific activity (328-609 Ci/mmol) by fluoride ion (n-Bu$\sb4$N$\sp{18}$F) displacement of a mesylate and triflate precursor. Preliminary studies on the unlabeled compounds showed them to have low lipophilicity and good receptor binding affinity; these results were reflected in the tissue distribution studies of the radiolabeled compounds with moderate selective uptake in target tissues (uterus, ovaries) and substantial receptor-mediated uptake in secondary tissues (thymus, muscle, kidney, fat).

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Bergmann, Kathryn Ellen

Contributors dc:contributor

• Katzenellenbogen, John A.

• Chemistry, Organic

Statement dc:rights

• Copyright 1993 Bergmann, Kathryn Ellen

Language dc:language

eng

Identifier

AAI9411566
(UMI)AAI9411566

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/21617