The use of biomacromolecules, e.g. peptides and antibodies, as therapeutics, so-called ‘biologics’, is experiencing an increase in interest as more and more small molecule therapeutics fail to meet the regulatory requirements for human use. To expedite the examination of such biologics as useful therapeutics, positron-emission tomography (PET) is being used as an early stage non-invasive in vivo imaging modality to rule in, or to rule out, candidates from the drug discovery pipeline. To realise this goal, small, reactive radiolabelled compounds, termed prosthetic groups, are often used to label the biologic of interest. Furthermore, prosthetic groups may also be incorporated into small molecule therapeutics, thus enabling rapid elucidation of candidates in a pre-clinical environment from a single appropriate prosthetic group precursor/apparatus set up. Diaryliodonium salts have been considered as useful precursors to prosthetic groups, as this class of compound may facilitate the one-step introduction of a nucleophilic radiolabel, e.g. [18F]fluoride ion, onto any position of a given arene. However, direction of the radiolabel onto the target arene is generally dictated by stereoelectronics, where the nucleophile is substituted upon the least electron-rich arene. To achieve this effect, electron-rich arenes, such as 2-thienyl, are employed. However, a potentiated product where the second arene is also electron-rich is the poorly characterised 2-[18F]fluorothiophene. To ensure that the products of radiofluorination processes reported herein are correctly assigned, an authentic sample of 2-[19F]fluorothiophene has been prepared on a 750 mmol scale (Scheme A). Scheme A: Synthesis of 2-[19F]fluorothiophene. Unambiguous verification of the detection of 2-[18F]fluorothiophene has herein been achieved for the first time by radiofluorination of the highly electrophilic electron-rich dithienyliodonium trifluoroacetate, using a microfluidic apparatus. iii Microfluidic apparatus is a technology which is experiencing an emergence as a useful means of probing the conditions advantageous to the production of radiolabeled material. We investigated the use of such apparatus in the optimised preparation of regioisomers of a key prosthetic group, [18F]fluorobenzaldehyde ([18F]FBA). The successful optimisation of the radiolabeling process has delivered 4-[18F]FBA in excellent radiochemical yields (>95%), as well delivering the associated regioisomer, 3-[18F]FBA, which is unavailable by convention means, by use of diaryliodonium salt precursors (Scheme B). Scheme B: Radiosynthesis of 4-[18F]FBA and 3-[18F]FBA from diaryliodonium salt precursors. Another prosthetic group considered bears the thiol reactive maleimide. An appropriate synthesis of a suitable diaryliodonium salt precursor (Scheme C) is reported herein. Scheme C: Synthesis of the precursor to the prosthetic group N-(4-[18F]fluorophenyl)maleimide.