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

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 Authors: Buck JR, Saleh S, Claus T, Lovly C, Hight MR, Nickels ML, Noor Tantawy M, Charles Manning H Abstract 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. PMID: 32631505 [PubMed - in process]
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research