Development of Novel Technetium-99m-Labeled Steroids as Estrogen-Responsive Breast Cancer Imaging Agents

Abstract

The goal of this project was the preparation and evaluation of new technetium-99m labeled compounds via utilization of their rhenium surrogates. An initial series of rhenium tricarbonyl complexes of estradiol were prepared using Stille coupling methods at the 17-alpha position of estradiol. While the compounds were chemically stable and retain modest affinity for the estrogen receptor compared to estradiol (2-10%), their ability to stimulate or inhibit estrogen function in cells was very low. As a result, the synthetic focus shifted to the 11-beta position of estradiol. Initial examples of 11-beta substituted estradiols were prepared which retained high affinity and potent antiestrogenic activity in cells. Newer rhenium tricarbonyl binding groups were also prepared which had the capability of ligation to the steroidal components using Huisgen [3+2] cycloaddition chemistry. The multi-step process for preparing the steroid component did not provide sufficient material at this time to evaluate the effectiveness of the ultimate steroid-metal binding target compounds.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2007
Accession Number
ADA474746

Entities

People

  • Robert N. Hanson

Organizations

  • Northeastern University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Bioassay
  • Breast Cancer
  • Carbonyl Complexes
  • Chemical Synthesis
  • Chemistry
  • Estrogens
  • Hormones
  • Materials
  • Medical Personnel
  • Metals
  • Organic Chemistry
  • Technetium
  • Transition Metals
  • United States

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Organic Chemistry
  • Systems Analysis and Design