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


METHODS
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.
Department of Radiation Oncology, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany. vasileios.askoxylakis@med.uni-heidelberg.de
Vasileios
V
Askoxylakis
Annabell
A
Marr
Annette
A
Altmann
Annette
A
Markert
Walter
W
Mier
Jürgen
J
Debus
Peter E
PE
Huber
Uwe
U
Haberkorn
D000595:Amino Acid Sequence; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D014162:Transfection; D014183:Transplantation, Heterologous
D055767:Immobilized Proteins; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D020797:Receptor, Platelet-Derived Growth Factor beta