Synthesis and Preclinical Evaluation of [18F]PF04217903, a Selective MET PET Tracer

Abstract

<p>The tyrosine kinase MET (hepatocyte growth factor receptor) is abnormally activated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (<b>1</b>) formed the basis for a bioisosteric replacement to the deoxyfluorinated analogue [<sup>18</sup>F]<b>2</b>, intended as a PET tracer for MET. [<sup>18</sup>F]<b>2 </b>could be synthesized with a “hydrous fluoroethylation” protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/µmol. <i>In vitro</i> autoradiography indicated that [<sup>18</sup>F]<b>2 </b>specifically binds to MET in PC3 tumor tissue, and <i>in vivo</i> biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs. </p>