Characterization of the radiosynthesis and purification of [18F]THK-5351, a PET ligand for neurofibrillary tau

Appl Radiat Isot. 2017 Dec:130:230-237. doi: 10.1016/j.apradiso.2017.10.002. Epub 2017 Oct 4.

Abstract

This work characterizes the radiochemical synthesis, purification, and formulation of [18F]THK-5351, a tau PET radioligand, and develops an automated radiosynthesis routine (ELIXYS, Sofie Biosciences). Nucleophilic radiofluorination reaction was complete by 7min at 110°C with radiochemical yields proportional to precursor mass (0.1-0.5mg). Optimized HPLC purification produced radiotracer product with no chemical impurities observed on analytical HPLC in formulation. Automated radiosynthesis (ELIXYS), HPLC purification and formulation was completed in 86min producing formulated product suitable for human research use.

Keywords: Alzheimer's disease; Automation; Formulation; Positron emission tomography; Radiochemical stability; Radiochemistry; THK; USP.

MeSH terms

  • Aminopyridines / chemical synthesis*
  • Aminopyridines / isolation & purification
  • Aminopyridines / metabolism
  • Chromatography, High Pressure Liquid / methods
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / metabolism
  • Humans
  • Neurofibrillary Tangles / metabolism
  • Positron-Emission Tomography*
  • Quinolines / chemical synthesis*
  • Quinolines / isolation & purification
  • Quinolines / metabolism
  • Radioligand Assay
  • Radiopharmaceuticals / isolation & purification*
  • Radiopharmaceuticals / metabolism
  • Solid Phase Extraction
  • tau Proteins / metabolism*

Substances

  • Aminopyridines
  • Fluorine Radioisotopes
  • Quinolines
  • Radiopharmaceuticals
  • THK5351
  • tau Proteins