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. READ ARTICLE

Bioorganic & Medicinal Chemistry Letters DOI:10.1016/j.bmcl.2020.127257

Authors: Jason R. Buck, Samir Saleh, Trey Claus, Christine Lovly, Matthew R. Hight, Michael L. Nickels, M. Noor Tantawy, H.Charles Manning

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