Synthesis of oncological [ 11 C]radiopharmaceuticals for clinical PET Filippo Lodi a, ⁎ , Claudio Malizia a , Paolo Castellucci c , Gianfranco Cicoria b , Stefano Fanti c , Stefano Boschi a a PET Radiopharmacy, Nuclear Medicine Unit, Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy b Medical Physics, Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy c PET Center, Nuclear Medicine Unit, Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy Received 22 June 2011; received in revised form 14 October 2011; accepted 22 October 2011 Abstract Positron emission tomography (PET) is a nuclear medicine modality which provides quantitative images of biological processes in vivo at the molecular level. Several PET radiopharmaceuticals labeled with short-lived isotopes such as 18 F and 11 C were developed in order to trace specific cellular and molecular pathways with the aim of enhancing clinical applications. Among these [ 11 C]radiopharmaceuticals are N-[ 11 C]methyl-choline ([ 11 C]choline), L-(S-methyl-[ 11 C])methionine ([ 11 C]methionine) and 1-[ 11 C]acetate ([ 11 C]acetate), which have gained an important role in oncology where the application of 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) is suboptimal. Nevertheless, the production of these radiopharmaceuticals did not reach the same level of standardization as for [ 18 F]FDG synthesis. This review describes the most recent developments in the synthesis of the above-mentioned [ 11 C]radiopharmaceuticals aiming to increase the availability and hence the use of [ 11 C]choline, [ 11 C]methionine and [ 11 C]acetate in clinical practice. © 2012 Elsevier Inc. All rights reserved. Keywords: Clinical PET; Oncology; [ 11 C]radiopharmaceuticals; Radiosynthesis; [ 11 C]choline; [ 11 C]methionine; [ 11 C]acetate 1. Introduction Positron emission tomography (PET) is a powerful nuclear medicine modality which provides imaging of biological processes in vivo [1]. This technique is based on administra- tion and detection of the biodistribution of radiopharmaceu- ticals labeled with positron-emitting radionuclides, allowing better quality imaging than conventional single-photon- emitting tomography, with higher sensitivity and good spatial resolution; also PET allows an accurate quantification of regional radiopharmaceutical concentration [2]. Several PET radiopharmaceuticals labeled with short- lived isotopes such as 18 F (t 1/2 =109.8 min) and 11 C (t 1/2 =20.4 min) were developed in order to visualize specific cellular and molecular pathways and then applied in oncology, neurology and cardiology [3–7]. In particular, 11 C is an attractive PET radionuclide because carbon is a ubiquitous element in biomolecules thus, [ 11 C]-labeling does not change the chemical structure and the biochemical properties in vivo. Moreover, the possibility to choose from different labeling positions in the same molecule provides the possibility to refine the radiopharmaceutical in terms of metabolic stability and nonspecific background ratio [8]. The short life of 11 C also enables comparative PET studies with the same [ 11 C]radiopharmaceutical (multitracer studies) in a short time frame with more favorable patient dosimetry [9]. On the other hand, the production of these radiopharmaceu- ticals must be performed in PET facilities with on-site cyclotrons and should be as fast as possible to reduce the loss of activity due to decay. In the last few years, [ 11 C]radiopharmaceuticals have gained increased importance in clinical PET, with relevant applications mainly in clinical oncology, in case of limitation of the gold standard PET radiopharmaceutical 2-[ 18 F]fluoro- 2-deoxy-D-glucose ([ 18 F]FDG), a glucose analogue used for staging, restaging and assessing the therapy response of a variety of tumors [10]. Among [ 11 C]radiopharmaceuticals, N-[ 11 C]methyl-choline ([ 11 C]choline), L-(S-methyl-[ 11 C]) methionine ([ 11 C]methionine) and 1-[ 11 C]acetate ([ 11 C] acetate) (Fig. 1) are widely used in clinical PET with Available online at www.sciencedirect.com Nuclear Medicine and Biology 39 (2012) 447 – 460 www.elsevier.com/locate/nucmedbio ⁎ Corresponding author. E-mail address: filippo.lodi@aosp.bo.it (F. Lodi). 0969-8051/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.nucmedbio.2011.10.016