An automated SPE-based high-yield synthesis of [ 11 C]acetate and [ 11 C]palmitate: no liquid–liquid extraction, solvent evaporation or distillation required ☆ Bruce H. Mock, Clive Brown-Proctor, Mark A. Green, Brandon Steele, Barbara E. Glick-Wilson, Qi-Huang Zheng ⁎ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202-2111, USA Received 28 April 2011; received in revised form 5 May 2011; accepted 13 May 2011 Abstract Introduction: An automated method is described for the rapid and high-yield synthesis of two of the most commonly used radioactive fatty acids: [ 11 C]acetate and [ 11 C]palmitate. Methods: Reaction of [ 11 C]CO 2 with the respective Grignard reagents in diethyl ether solution proceeded for 2 min at 40°C. Quenching of the reaction and liberation of nonreacted [ 11 C]CO 2 occurred upon addition of a fourfold molar excess of aqueous 0.1 M HCl (acetate) or nonaqueous HCl/Et 2 O (palmitate). Labeled products were then purified by adsorption to an Alumina-N Sep-Pak Plus cartridge and eluted with either aqueous NaH 2 PO 4 solution (acetate) or 100% ethanol (palmitate). Results: High-performance liquid chromatography analysis confirmed that the radiochemical purity of each product was N98%, and decay- corrected radiochemical yields averaged 33% for [ 11 C]palmitate and 40% for [ 11 C]acetate. Conclusion: The method requires no liquid–liquid extraction, solvent evaporation or distillation capabilities and can be readily adapted to existing radiosynthesis modules. © 2011 Elsevier Inc. All rights reserved. Keywords: [ 11 C]Acetate; [ 11 C]Palmitate; Grignard reagent; Solid-phase extraction (SPE); Automation; Positron emission tomography (PET) 1. Introduction Even though each of these radiopharmaceuticals has a 30+ year history, [ 11 C]acetate and [ 11 C]palmitate still attract great interest from radiochemists and investigators who wish to study myocardial metabolism by positron emission tomography (PET) [1]. However, the published methods for the production of [ 11 C]acetate require purification of the final product by liquid–liquid extraction [2], distillation [3,4] or ion exchange column chromatography [5]. As for [ 11 C] palmitate, the production approaches include column chro- matography [6], liquid–liquid extraction [7], a captive solvent method [8], a hydrophobic membrane method [9], column extraction [10] and solid-phase extraction (SPE) [11,12]. Most of these approaches make the development of an automated protocol difficult and complicated, especially if the available radiosynthesis module cannot easily be modified. In addition, there are gaps in radiosynthetic detail among the published methods, and certain key steps were difficult to repeat in our hands or gave poor or widely variable radiochemical yields. To address local investigator needs for [ 11 C]palmitate- PET, we initially sought to adapt established literature methods [6–12] to our in-house multipurpose C-11 radio- synthesis module [13]. An abbreviated layout of our module is diagramed in Fig. 1. Our first efforts were to identify the essential parameters of the reaction between n-pentadecyl- magnesium bromide and [ 11 C]CO 2 . For example, what were the optimal volume and molar concentration of the Grignard reagent that could effectively trap incoming [ 11 C]CO 2 , yet Available online at www.sciencedirect.com Nuclear Medicine and Biology 38 (2011) 1135 – 1142 www.elsevier.com/locate/nucmedbio ☆ This project was supported by the Department of Radiology and Imaging Sciences at Indiana University School of Medicine. ⁎ Corresponding author. Tel.: +1 317 278 4671; fax: +1 317 278 9711. E-mail address: qzheng@iupui.edu (Q.-H. Zheng). 0969-8051/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.nucmedbio.2011.05.007