Preparation of Conjugates for Affibody-Based PNA-Mediated Pretargeting

Methods Mol Biol. 2020:2105:283-304. doi: 10.1007/978-1-0716-0243-0_18.

Abstract

Affibody molecules are small engineered scaffold proteins suitable for in vivo tumor targeting. Radionuclide molecular imaging using directly radiolabelled affibody molecules provides excellent imaging. However, affibody molecules have a high renal reabsorption, which complicates their use for radionuclide therapy. The high renal reabsorption is a common problem for the use of engineered scaffold proteins for radionuclide therapy. Affibody-based PNA-mediated pretargeting reduces dramatically the absorbed dose to the kidneys and makes affibody-based radionuclide therapy possible. This methodology might, hopefully, solve the problem of high renal reabsorption for radionuclide therapy mediated by other engineered scaffold proteins.

Keywords: 111In; 177Lu; 57Co; 68Ga; Affibody molecules; PNA; Peptide synthesis; Pretargeting; Scaffold protein; Sortase A.

MeSH terms

  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Gene Expression
  • Gene Targeting*
  • Humans
  • Isotope Labeling
  • Molecular Imaging
  • Molecular Probes
  • Nucleic Acid Hybridization
  • Peptide Nucleic Acids / administration & dosage*
  • Peptide Nucleic Acids / chemical synthesis
  • Peptide Nucleic Acids / chemistry
  • Peptide Nucleic Acids / isolation & purification
  • Recombinant Fusion Proteins* / chemistry
  • Solid-Phase Synthesis Techniques

Substances

  • Molecular Probes
  • Peptide Nucleic Acids
  • Recombinant Fusion Proteins