Synthesis of a [ 18 F]‐labeled ceritinib analogue for positron emission tomography of anaplastic lymphoma kinase, a receptor tyrosine kinase, in lung cancer

Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non‐invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [ 18 F]fluoroethyl‐ceritinib ([ 18 F]‐FEC), for use with positron emission tomography. We used two methods to synthesize [ 18 F]‐FEC. First, [ 18 F]fluoroethyl‐tosylate was prepared, coupled with ceritinib, and the product purified to yield [ 18 F]‐FEC. Alternatively, a precursor compound was synthesized, directly fluorinated with 18 F‐fluoride, and purified to yield [ 18 F]‐FEC. The first method produced [ 18 F]‐FEC with an average decay‐corrected yield of 24% ( n  = 4), specific activity of 1200 mCi/µmol, and >99% purity; synthesis time was 115 min from the end of bombardment. The second method produced [ 18 F]‐FEC with an average yield of 7% ( n  = 4), specific activity of 1500 mCi/µmol, and >99% purity; synthesis time was 65 min from the end of bombardment. The synthesis of a novel 18 F‐labeled analogue of ceritinib has been achieved in acceptable yields, at high purity, and with high specific activity. The compound is a potential positron emission tomography imaging agent for the detection of ALK‐overexpressing solid tumors such as lung cancer.