Development of novel tumor imaging agents with phage-display combinatorial peptide libraries.

Published

Journal Article

RATIONALE AND OBJECTIVES: Current radiologic methods do not provide sufficient information for unambiguous diagnosis and prognosis of cancer. The present investigation sought to address this deficiency by developing a system for designing novel small molecules targeted against tumor-specific molecules for use as radionuclide imaging agents. MATERIALS AND METHODS: Part of a tumor-specific receptor, purified recombinant epidermal growth factor receptor (EGFR), variant III, extracellular domain (rEGFRvIII-ecd), was used as the target in the selection of EGFRvIII-specific peptide ligands from random peptide bacteriophage (phage) display libraries. After three rounds of screening, phage isolates were tested for binding affinity with an enzyme-linked immunosorbent assay. Positive phage were sequenced, and the peptides were synthesized and tested for binding affinity with a surface plasmon resonance assay. RESULTS: Affinity screening identified 49 peptide-expressing phage that showed enhanced binding to the variant receptor compared with wild-type EGFR. Free peptides from the two phage isolates exhibiting the most favorable binding were tested for target binding. One of these demonstrated a binding affinity for rEGFRvIII-ecd in the 30-nmol/L range. CONCLUSION: These data suggest that phage display libraries may be very useful in the design of novel, high-affinity tumor imaging agents.

Full Text

Duke Authors

Cited Authors

  • Campa, MJ; Serlin, SB; Patz, EF

Published Date

  • August 2002

Published In

Volume / Issue

  • 9 / 8

Start / End Page

  • 927 - 932

PubMed ID

  • 12186442

Pubmed Central ID

  • 12186442

Electronic International Standard Serial Number (EISSN)

  • 1878-4046

International Standard Serial Number (ISSN)

  • 1076-6332

Digital Object Identifier (DOI)

  • 10.1016/s1076-6332(03)80463-4

Language

  • eng