Development of solid phase-based PET isotope labelling methods
Jameson, Elizabeth Frances Mary
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Positron Emission Tomography (PET) has great value in research and clinical applications from oncology to neurodegenerative disorders. However, there is a barrier in translating biological knowledge into new PET applications due in part to the lack of efficient, widely applicable methods for labelling compounds with PET radioisotopes. Herein, a generic approach to radiolabelling is presented which is direct, broadly applicable and potentially adaptable to either of the two most commonly used PET radioisotopes, 11C and 18F. This approach employs the advantages of solid phase synthesis to achieve selective release of only the desired radiolabelled product from a solid support in a single step, simplifying purification and hence improving synthetic efficiency. Polystyrene resin was functionalised with a 1,2-diol group; this allowed the covalent attachment of compounds bearing boronic acid groups via formation of a boronate ester linkage. A Suzuki-Miyaura reaction with methyl iodide was used to cleave a model compound from the resin in 61% conversion after five minutes. This reaction was adapted to develop a fully automated radiosynthesis with [11C]- methyl iodide which generated a radiolabelled model compound in 2 – 7% non-decay-corrected radiochemical yield. This provided proof of concept for the simultaneous cleavage of compounds from the resin and radiolabelling with 11C. A boronic acid precursor of the known radiotracer [11C]-M-MTEB was attached to the resin and successfully radiolabelled with 11C in 2.4% non-decay-corrected radiochemical yield and 96 – 100% radiochemical purity under the same conditions. Furthermore, the potential adaptability of this solid phase approach to 18F radiolabelling was demonstrated by treatment of the resin-bound small molecules and peptides with potassium bifluoride, which released the compounds rapidly as trifluoroborate salts.