title: Preclinical evaluation of the breast cancer cell-binding peptide, p160.
abstract: OBJECTIVE
  Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a peptide-based radiopharmaceutical, we investigated the properties of a peptide with affinity for human breast cancer, which has been selected through phage display.
  
  
  METHODS
  The bioactivity of the p160 peptide (VPWMEPAYQRFL) was evaluated in vitro and in vivo. The specific binding to human breast cancer MDA-MB-435 cells was confirmed in competition experiments. Internalization of the peptide was investigated with confocal microscopy. Furthermore, the biodistribution of (131)I-labeled p160 was studied in tumor-bearing mice. In vivo stability was evaluated at different periods after tracer administration using high-performance liquid chromatography analysis.
  
  
  RESULTS
  The binding of (125)I-labeled p160 was inhibited up to 95% by the unlabeled peptide with an IC(50) value of 0.6 micromol/L. In addition, 40% of the total bound activity was found to be internalized into the human breast cancer cells. Although a rapid degradation was seen, biodistribution studies in nude mice showed a higher uptake in tumor than in most of the organs. Perfusion of the animals caused a reduction of the radioligand accumulation in the healthy tissues, whereas the tumor uptake remained constant. A comparison of [(131)I]p160 with a (131)I-labeled Arg-Gly-Asp peptide revealed a higher tumor-to-organ ratio for [(131)I]p160.
  
  
  CONCLUSIONS
  p160 has properties that make it an attractive carrier for tumor imaging and the intracellular delivery of isotopes or chemotherapeutic drugs.
authors.affiliation: Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, University of Heidelberg, Germany.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Askoxylakis
authors.forename: Sabine
authors.initials: S
authors.lastname: Zitzmann
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Keith
authors.initials: K
authors.lastname: Graham
authors.forename: Susanne
authors.initials: S
authors.lastname: Krämer
authors.forename: Frederic
authors.initials: F
authors.lastname: von Wegner
authors.forename: Rainer H A
authors.initials: RH
authors.lastname: Fink
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwab
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000378:metabolism / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000378:metabolism* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D009842:Oligopeptides; D015282:Octreotide