title: Identification and evaluation of a new tumor cell-binding peptide, FROP-1.
abstract: Peptides are useful tools for the targeted delivery of radionuclides or chemotherapeutic drugs to their site of action within an organism. Given that the peptide receptor is overexpressed at the tumor, therapeutically active doses can be delivered to the tumor with reduced side effects. Because currently known peptides are restricted to a small number of tumors, new molecules and their corresponding receptors have to be identified to enlarge the spectrum of malignancies that can be diagnosed or treated using tumor-targeting peptides.
  
  
  METHODS
  A 12-amino-acid peptide phage display system was applied to identify a new peptide binding to follicular thyroid carcinoma cells. The properties of the radiolabeled peptide were assessed in binding, competition, and internalization experiments in a variety of tumor cell lines including FRO82-2 and MCF-7 cells, and the pharmacokinetic behavior of the radiolabeled peptide was evaluated in tumor-bearing mice. Peptide stability was studied in human serum.
  
  
  RESULTS
  After 5 selection rounds, the new peptide, FROP-1 (EDYELMDLLAYL), was identified. It showed binding to follicular thyroid carcinoma as well as anaplastic thyroid carcinoma, mammary carcinoma, cervix carcinoma, prostate carcinoma, and cell lines derived from head and neck tumors, and low affinity could be observed to control cells such as human umbilical vein endothelial cells or immortalized keratinocytes. In MCF7 cells, 78% and 86% of the bound activity was internalized after 10 and 60 min of incubation, respectively. Stability experiments in human serum showed the appearance of a degradation product after 15 min. Tumor uptake of the radioactive labeled peptide increased for 45 min in nude mouse models, reaching an accumulation level of approximately 3.6 percentage injected dose (%ID)/g for FRO82-2 tumors or approximately 3.8 %ID/g for MCF-7 tumors.
  
  
  CONCLUSIONS
  The target of FROP-1 is most likely a molecule found generally in tumors, making this peptide highly attractive for diagnostic or therapeutic applications. However, modifications are needed to increase stability and affinity.
authors.affiliation: Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany. sabine.zitzmann@schering.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Zitzmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Krämer
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hebling
authors.forename: Annette
authors.initials: A
authors.lastname: Altmann
authors.forename: Axel
authors.initials: A
authors.lastname: Rother
authors.forename: Dietmar
authors.initials: D
authors.lastname: Berndorff
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000000981:diagnostic imaging*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000493:pharmacokinetics*; D019151:Peptide Library; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: C521499:FROP-1 peptide; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D019151:Peptide Library; D019275:Radiopharmaceuticals