Development of Cell Type-Specific Contrast Agents for Magnetic Resonance Imaging of Breast Tumors

Abstract

Magnetic Resonance Imaging is an emerging diagnostic tool for breast cancer that provides high-resolution three-dimensional images of tissues. A significant increase of specificity of detection of cancerous lesions could be achieved by use of tumor specific contrast agents (CA). Currently, tumor-specific targeting of CA is achieved by antibodies (Ab) or fragments thereof. The major disadvantages of Ab are their large size and ability to induce immune response. We proposed to use DNA aptamers for tumor-specific targeting of CA because short DNA molecules are smaller than Ab, have better tissue penetration and are non-toxic and non-immunogenic. During the study, PSI developed an experimental system and generated essential reagents for selection of DNA aptamers. Expression constructs encoding human EGF receptor (EGF-R) fusion protein were produced and used for generation of stable cell lines expressing this protein at suitable levels. EGF-R was used for isolation of DNA aptamers from combinatorial synthetic library. A group of structurally related aptamers was identified. In the course of the program a variety of technical challenges were identified and alternative approaches were undertaken. Full characterization and validation of the isolated EGF-R-specific aptamers was not completed. PSI research effort generated valuable reagents and technical knowledge for further development of the proposed technology.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2008
Accession Number
ADA481192

Entities

People

  • Anton Chestukhin

Organizations

  • Physical Sciences (United States)

Tags

DTIC Thesaurus Topics

  • Antibodies
  • Breast Cancer
  • Cell Line
  • Cell Membrane
  • Cells
  • Contrast
  • Demographic Cohorts
  • Detection
  • Magnetic Resonance
  • Magnetic Resonance Imaging
  • Molecules
  • Neoplasms
  • Proteins
  • Recombinant Proteins
  • Resonance
  • Schematic Diagrams
  • Targeting

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).