A simplified radiosynthesis of [ 18 F]MK-6240 for tau PET imaging

J Labelled Comp Radiopharm. 2019 Feb;62(2):109-114. doi: 10.1002/jlcr.3695. Epub 2018 Dec 19.

Abstract

[18 F]MK-6240 (6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is a highly selective PET radiotracer for the in vivo imaging of neurofibrillary tangles (NFTs). [18 F]MK-6240 was synthesized in one step from its bis-Boc protected precursor N-[(tert-butoxy)carbonyl]-N-(6-nitro-3-[1H-pyrrolo[2,3-c]pyridin-1-yl]isoquinolin-5-yl) carbamate in DMSO using [18 F] fluoride with TEA HCO3 with step-wise heating up to 150°C, resulting in an isolated radiochemical yield of 9.8% ± 1.8% (n = 3) calculated from the end of bombardment (5.2% ± 1.0% calculated from the end of synthesis). This new synthetic approach eliminates the acidic deprotection of the bis-Boc 18 F-labeled intermediate, which reduces the number of operations necessary for the synthesis as well as losses, which occur during deprotection and neutralization of the crude product mixture prior to the HPLC purification. The synthesis was performed automatically with a single-use cassette on an IBA Synthera+ synthesis module. This synthesis method affords the radioligand with a reliable radiochemical yield, high radiochemical purity, and a high molar activity. [18 F]MK-6240 synthesized with this method has been regularly (n > 60) used in our ongoing human and animal PET imaging studies.

Keywords: Alzheimer disease; MK-6240; NFTs; tau.

MeSH terms

  • Chemistry Techniques, Synthetic / instrumentation
  • Chemistry Techniques, Synthetic / methods
  • Fluorine Radioisotopes / chemistry*
  • Isoquinolines / chemistry*
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / chemical synthesis*
  • tau Proteins / metabolism

Substances

  • Fluorine Radioisotopes
  • Isoquinolines
  • MK-6240
  • Radiopharmaceuticals
  • tau Proteins