[C-11] carbon disulfide : a versatile radiolabelling reagent for the development of PET tracers

• Main Author: Haywood, Thomas
• Other Authors: Miller, Philip
• Published: Imperial College London 2015
• Subjects: 546
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.689097

This thesis is concerned with the development and implementation of 11C carbon disulfide as a method of radiolabelling molecules to form radiotracers for application in positron emission tomography (PET). The development of the synthetic route to [11C] carbon disulfide is described. The preferred synthesis method for the main body of this work was to pass [11C] methyl iodide over sulfur at high temperature. Other methods of [11C] carbon disulfide production were also explored including synthesis from [11C] methane and also direct synthesis in the cyclotron target. Following the improved and robust synthesis of [11C] carbon disulfide a series of radiolabelled thiourea compounds were synthesised from the reaction of [11C] carbon disulfide and amines. This thiourea production method was further developed into the synthesis of 2 potential radiotracers. The progestin inhibitor tanaproget, and the CXCR4 inhibitors IT1a and IT1t which are still undergoing synthetic development. As well as [11C] carbon disulfide, [11C] ammonium thiocyanate was also explored as a potential [11C] radiolabelling reagent, with interest paid to its nucleophilic properties. Ammonium thiocyanate formed from the reaction of carbon disulfide with ammonia in solution. A series of [11C] phenacyl thiocyanate compounds were synthesised from the reaction of [11C] ammonium thiocyanate and acetophenone precursors. These [11C] radiolabelled phenacyl thiocyanates were reacted on to form a series of analogous radiolabelled thiazole compounds. Once a more comprehensive understanding of the chemistry surrounding [11C] carbon disulfide had been established, a series of experiments were carried out in order to trap [11C] carbon disulfide on a cooled microfluidic device (MFD) before passing a droplet of precursor along the reaction channel of the MFD to react with the trapped [11C] carbon disulfide, forming the desired product, in this case monocyclohexyldithiocarbamate cyclohexylammonium salt. The final chapter, while not directly related to PET applications investigates the use of microfluidic and ow systems for the homogeneous and heterogeneous hydrogenation of a range of alkanes. The hydrogenation of styrene to ethylbenzene was used as a model reaction of the testing of various experimental set-ups including stopped ow, and continuous flow in a range of flow systems. During annular ow experiments in a microfluidic device the deposition of a rhodium deposit was also collected and analysed for its catalytic properties.