Improved automated synthesis of [ 18 F]fluoroethylcholine as a radiotracer for cancer imaging M. Piel, a, * A. Bauman, a R. P. Baum, b S. Ho ¨ hnemann, a I. Klette, b R. Wortmann b and F. Ro ¨sch a a Institute of Nuclear Chemistry, Johannes Gutenberg-Universita ¨ t Mainz, 55128 Mainz, Germany b Department of Nuclear Medicine/PET Centre, Zentralklinik Bad Berka, 99437 Bad Berka, Germany Received 17 October 2006; revised 15 February 2007; accepted 20 February 2007 Available online 22 February 2007 Abstract—[ 18 F]Fluoroethylcholine has been recently introduced as a promising 18 F-labelled analogue of [ 11 C]choline which had been previously described as a tracer for metabolic cancer imaging with positron emission tomography (PET). Due to the practical advantages of using the longer-lived radioisotope 18 F(t 1/2 = 110 min), offering the opportunity of a more widespread clinical application, we established a reliable, fully automated synthesis for its production using a modified, commercially available module. [ 18 F]Fluoroethylcholine was prepared from N,N-dimethylaminoethanol by iodide catalyzed alkylation with 1-[ 18 F]fluoro-2- tosylethane as alkylating agent, resulting in a total radiochemical yield of 30 ± 6% after a synthesis time of 50 min. The specific activity of [ 18 F]fluoroethylcholine was >55 GBq/lmol and the radiochemical purity 95–99%. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction Many tumours are characterized by an enhanced cell proliferation. This is usually associated with an elevated uptake and phosphorylation of choline to form choline phosphate which is used in the synthesis of membrane phospholipids. 1–3 31 P magnetic resonance spectroscopy has confirmed this hypothesis by showing higher levels of choline phosphate in different tumour entities. Therefore, [ 11 C]choline was developed and has shown its clinical potential in the evaluation of brain tumours, oesophageal carcinoma and prostate cancer 4–6 using PET. Because of the short half-life of 11 C (t 1/2 = 20.38 min), resulting in a limited usefulness for clini- cal routine, different 18 F-labelled (t 1/2 = 109.7 min) analogues were synthesized to overcome this problem. Shown in Figure 1 are the most prominent choline derivatives. [ 18 F]fluorocholine ([ 18 F]FCh) (2), first introduced by DeGrado et al., 7 is synthesized by reacting N,N-dimeth- ylaminoethanol (DMAE) with [ 18 F]fluoro-bromome- thane ([ 18 F]FBM). This labelling synthon has to be cleaned up via gas chromatographic purification, which is not a standard operation in radiopharmaceutical laboratories. 8 A simple and more convenient way of synthesizing choline analogue compounds is the 18 F-fluoroethylation of N,N-dimethylaminoethanol, leading to [ 18 F]fluoroethylcholine ([ 18 F]FECh) (3). The production route of 18 F-fluoroethylating synthons, espe- cially1-[ 18 F]fluoro-2-tosylethane ([ 18 F]FETos), is a sim- ple, very reliable procedure and can be established in a fully automated way without any demanding purifica- tion steps (Fig. 2). Comparing the chemical structure differences between [ 18 F]FCh (2) and [ 18 F]FECh (3), it is obvious that [ 18 F]FCh (2) is more similar to [ 11 C]Cho (1), than [ 18 F]FECh (3) is. Deves and Krupka, 9 as well as Clary 0968-0896/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.bmc.2007.02.038 Keywords: [ 18 F]Fluoroethylcholine; 18 F-Fluoroalkylation; Positron emission tomography. * Corresponding author. Tel.: +49 6131 3925371; fax: +49 6131 3925253; e-mail: piel@mail.uni-mainz.de N H 3 11 C OH N OH 18 F N OH 18 F (1 ) (2 ) (3 ) Figure 1. Structure of [ 11 C]choline (1 ,[ 11 C]Cho) and the 18 F-fluori- nated analogues [ 18 F]fluorocholine (2 , FCh) and [ 18 F]fluoroethylcho- line (3 , FECh). Bioorganic & Medicinal Chemistry 15 (2007) 3171–3175