Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

Abstract

We have proposed to develop tethered Hsp90 inhibitor capable of carrying various radioactive iodine isotopes for early detection and ablation of metastatic breast cancers. These probes specifically target a surface form of heat shock protein 90 (eHsp90)that is expressed on malignant cells and internalized. In this report we describe our chemistry efforts to synthesize a non-radioactive tethered Hsp90 inhibitor, methods developed for stannylation of the molecule such that it can be effectively radioiodinated with either I121 or I124. Two paths of synthesis were developed. A standard operating procedure was developed and transferred to our collaborator who developed protocols for radioiodination. An in active control molecule was also developed. These molecules will be tested as imaging agents in mouse models of breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2017
Accession Number
AD1046568

Entities

People

  • Mike Zalutsky
  • Timothy Haystead

Organizations

  • Duke University

Tags

DTIC Thesaurus Topics

  • Ablation
  • Amino Acids
  • Breast Cancer
  • Cancer
  • Chemical Synthesis
  • Chemistry
  • Detection
  • Diseases And Disorders
  • Dyes
  • Formic Acid
  • Inhibitors
  • Isotopes
  • Molecules
  • Neoplasms
  • Organic Chemistry
  • Radiotherapy

Fields of Study

  • Chemistry

Readers

  • Molecular Biology and Genetics
  • Nanoscale Plasmonic Nanotechnology
  • Neurotoxicology