Peptide-Based Targeting of the Platelet-Derived Growth Factor Receptor Beta

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 ¹²⁵I or ¹³¹I. 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.