Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide

Appl Radiat Isot. 2016 Oct:116:120-7. doi: 10.1016/j.apradiso.2016.07.023. Epub 2016 Jul 27.

Abstract

2-[(18)F]-Fluoro-3-pyridinecarboxaldehyde ([(18)F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the product of the reaction with FPCA has been fully characterised. In-vivo biodistribution of [(18)F]RI-OR2-TAT has been measured in Wistar rats.

Keywords: Aβ peptide; Chemical ligation; Oxime bond; PET; [(18)F]F prosthetic group.

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Protein Binding
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Robotics / methods
  • Tissue Distribution

Substances

  • Amyloid beta-Peptides
  • Fluorine Radioisotopes
  • Pyridines
  • Radiopharmaceuticals
  • pyridinecarboxaldehyde
  • Fluorine-18