N-[18F]-Fluoroacetylcrizotinib: A potentially potent and selective PET tracer for molecular imaging of non-small cell lung cancer

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127257. doi: 10.1016/j.bmcl.2020.127257. Epub 2020 Jun 2.


N-[18F]fluoroacetylcrizotinib, a fluorine-18 labeled derivative of the first FDA approved tyrosine kinase inhibitor (TKI) for the treatment of Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), crizotinib, was successfully synthesized for use in positron emission tomography (PET). Sequential in vitro biological evaluation of fluoracetylcrizotinib and in vivo biodistribution studies of [18F]fluoroacetylcrizotinib demonstrated that the biological activity of the parent compound remained unchanged, with potent ALK kinase inhibition and effective tumor growth inhibition. These results show that [18F]fluoroacetylcrizotinib has the potential to be a promising PET ligand for use in NSCLC imaging. The utility of PET in this context provides a non-invasive, quantifiable method to inform on the pharmacokinetics of an ALK-inhibitor such as crizotinib prior to a clinical trial, as well as during a trial in the event of acquired drug resistance.

Keywords: Cancer; Crizotinib; NSCLC; PET; Therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crizotinib / chemical synthesis
  • Crizotinib / chemistry*
  • Crizotinib / pharmacology
  • Dose-Response Relationship, Drug
  • Fluorine Radioisotopes
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / metabolism
  • Molecular Imaging*
  • Molecular Structure
  • Positron-Emission Tomography*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Structure-Activity Relationship


  • Fluorine Radioisotopes
  • Protein Kinase Inhibitors
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Fluorine-18