Synthesis of novel peptide nucleic acid-peptide chimera for non-invasive imaging of cancer

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):409-14. doi: 10.1081/ncn-200061865.

Abstract

A chelator-peptide-PNA-peptide chimera specific for KRAS has been prepared by continuous solid phase coupling with a C-terminal insulin-like growth factor 1 (IGF1) ligand, D(cys-ser-lys-cys), and N-terminal bis(S-benzoyl thioglycoloyl) diaminopropanoate chelator for radionuclide labeling. The probe was purified by RP-HPLC and characterized by MALDI-TOF mass spectroscopy. The probe was labeled with 99mTc and 64Cu. Both labeled probes accumulated in human pancreatic cancer xenografts in immunocompromised mice. Control experiments with mismatch chimeras and control xenografts will be necessary to determine the specificity of this molecular diagnostic strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Copper Radioisotopes / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Ligands
  • Mice
  • Mice, Nude
  • Models, Chemical
  • Neoplasm Transplantation
  • Neoplasms / diagnosis*
  • Neoplasms / pathology*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / pathology
  • Peptide Nucleic Acids / chemistry*
  • Peptides / chemistry*
  • Positron-Emission Tomography / instrumentation*
  • Protein Structure, Tertiary
  • Radionuclide Imaging / instrumentation*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Technetium / chemistry
  • Time Factors

Substances

  • Chelating Agents
  • Copper Radioisotopes
  • Ligands
  • Peptide Nucleic Acids
  • Peptides
  • Insulin-Like Growth Factor I
  • Technetium