Mian M. Alauddin
University of Texas MD Anderson Cancer Center, USA
Title: Synthesis of a [18F]-labeled ceritinib analogue for positron emission tomography of anaplastic lymphoma kinase, a receptor tyrosine kinase, in lung cancer
Biography
Biography: Mian M. Alauddin
Abstract
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 approval for therapy, non-invasive indicators of target engagement or predictive biomarkers in vivo are lacking. We designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [18F]fluoroethyl-ceritinib, (]18F]-FEC), for use with positron emission tomography (PET). We used two methods to synthesize [18F]-FEC. Method 1: [18F]fluoroethyl-tosylate was prepared by radiofluorination of ethylene glycol di-tosylate, purified by HPLC and coupled with ceritinib at 120oC. The product was purified by flash chromatography to yield [18F]-FEC. Alternatively, a precursor compound, chloroethyl-ceritnib, was synthesized and fluorinated with K18F/kryptofix. The product was purified by HPLC or flash chromatography to yield [18F]-FEC. Method 1 produced [18F]-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 (EOB). Method 2 produced [18F]-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 EOB. Of these two methods, we judged Method 1 to be the better choice for producing a pure compound for biological applications. Synthesis of a novel [18F]ceritinib analogue has been achieved in good yields, with high purity and specific activity. The compound is a potential PET imaging agent for the detection of ALK overexpressing solid tumors, such as lung cancer, and should be tested in vitro and in vivo.
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