Peptide-based targeting of the platelet-derived growth factor receptor beta

Mol Imaging Biol. 2013 Apr;15(2):212-21. doi: 10.1007/s11307-012-0578-7.

Abstract

Purpose: The aim of this work is to identify new ligands targeting the platelet-derived growth factor receptor beta (PDGFRβ).

Procedures: Biopanning was carried out with a 12-amino-acid phage display library against the recombinant extracellular domain of PDGFRβ. The identified peptide PDGFR-P1 was chemically synthesized and labeled with (125)I or (131)I. In vitro studies were performed on the PDGFRβ-expressing cell lines BxPC3 and MCF7 and on PDGFRβ-transfected HEK cells in comparison to negative control wtHEK293 and CaIX-transfected HEK cells. Biodistribution experiments were performed in Balb/c nude mice, carrying subcutaneously BxPC3 tumors.

Results: In vitro studies demonstrated a higher binding to BxPC3, MCF7, and PDGFRβ-tr-HEK cells in comparison to negative control cell lines. Binding was inhibited up to 90% by the unlabeled PDGFR-P1 peptide. Organ distribution studies revealed a higher accumulation in BxPC3 tumors than in most organs.

Conclusions: PDGFR-P1 is a promising candidate for targeting human PDGFRβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Delivery Systems / methods
  • Drug Discovery / methods
  • Female
  • HEK293 Cells
  • Humans
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / metabolism
  • Ligands
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Pancreatic Neoplasms / metabolism
  • Peptide Library
  • Peptides / chemistry*
  • Peptides / pharmacokinetics*
  • Receptor, Platelet-Derived Growth Factor beta / chemistry
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / pharmacokinetics
  • Transfection
  • Transplantation, Heterologous

Substances

  • Immobilized Proteins
  • Ligands
  • Peptide Library
  • Peptides
  • Receptor, Platelet-Derived Growth Factor beta