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Title: Novel carbon-11 radiolabelling of organic and inorganic compounds using [¹¹C]CS₂ : towards applications in pet imaging
Author: Cesarec, Sara
ISNI:       0000 0005 0287 1421
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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This thesis investigates the reaction of [11C]carbon disulfide and ammonium [11C]thiocyanate for the preparation of 11C-labelled organic and inorganic molecules that have the potential to be used in positron emission tomography (PET) imaging. CS2 is a small and reactive molecule that, to date, has not been widely explored for the generation of 11C-labelled compounds. CS2 is known to react rapidly with amines and to form dithiocarbamate (DTC) molecules within minutes. This method therefore presents a facile route for quickly generating 11C-labelled molecules. Herein, [11C]CS2 was produced by passing [11C]methyl iodide over sulfur at 450°C, and reacted with a series of amines to generate the corresponding radiolabelled [11C]DTC molecules in high radiochemical yields (RCYs). For the first time, these [11C]DTC molecules have been used to efficiently and rapidly generate a series of Pd, Pt and Au radiolabelled DTC complexes, such as [Pd([11C]S2CNEt2)(dppp)][Cl] and [AuCl2([11C]S2CNEt2)], in high RCYs and purity. Unlabelled DTC reference complexes were prepared and their structures confirmed by NMR and in some cases by X-ray crystallography. Ammonium [11C]thiocyanate was also investigated as a radiolabelling reagent. It is a potent nucleophile and therefore has the potential to be applied to a wide range of nucleophilic substitution reactions. [11C]NH4SCN was prepared via reaction of ammonia with [11C]carbon disulfide under reflux. Previously, [11C]NH4SCN was used to successfully radiolabel phenacyl thiocyanate and thiazole molecules. In an extension to this method, a carbohydrate derivative, mannose [11C]thiocyanate, was radiolabelled in RCYs of 86 % by the reaction of [11C]NH4SCN with mannose triflate. This is of particular interest as this method provides a novel route to radiolabelling carbohydrate derivatives with carbon-11 via a nucleophilic method. Furthermore, glucose [11C]thiocyanate derivatives may be expected to behave in a similar way to [11F]FDG. [11C]NH4SCN was also investigated as a potential cyanating reagent, thus potentially avoiding the need for [11C]HCN production which requires elaborate synthesis and specialised equipment. A series of alkyl and aromatic nitriles were synthesised via two different methods that were tested for 11C-labelling. Unfortunately, this 11C-labelling procedure proved inconclusive, most likely due to the slow rates of these reactions within the short timeframes required for carbon-11 labelling.
Supervisor: Miller, Philip Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral