An integrated approach to hyperpolarised magnetic resonance

Nuclear magnetic resonance spectroscopy (NMR) and Magnetic Resonance Imaging (MRI) play a vital role in science and medicine. Hyperpolarisation technologies, which amplify achievable signal, can unlock new MR applications. Here, a group of thienopyridazines were synthesised and hyperpolarised via Signal Amplification by Reversible Exchange (SABRE). Thienopyridazines are of medical interest due to their anti-cancer properties. 1H-NMR signal enhancements of 10,130-fold ± 230 at 9.4 T (~33% polarisation) were achieved, under optimal conditions and novel 15N-labelling used to identify eight SABRE active complexes. Alongside high polarisation levels, long signal lifetimes are desired to warrant a longer window for MR observation. 1H T1 lifetimes for the thienopyridazines were found to be ~18-40 s. Long-lived state (LLS) approaches extended the magnetic lifetime of the shorter T1 values to 40 s in the T[2,3-d]P regioisomer. Following successful hyperpolarisation, the imaging potential of thienopyridazines was demonstrated. In vivo detection of a 2 mL bolus of hyperpolarised thienopyridazine (in organic solvent) injected into the subcutaneous space was accomplished. Although hyperpolarised signal in a non-toxic aqueous solution was proven feasible (through biphasic extraction), polarisation levels were lower (3%); thus in vivo detection following intravenous injection was not possible. Although SABRE excels in 1H polarisation, imaging is confounded by the vast background signals from the water/fat pool. Successful X-nuclei imaging utilised hyperpolarised 13C-nicotinamide (via SABRE & dissolution Dynamic Nuclear Polarisation, d-DNP). d-DNP achieved 13C polarisation levels of 13% (with apparent 15 s T1) permitting easy detection in an in vivo cancer model. Equivalent SABRE polarisation was inferior (~0.17%) and only in vitro imaging was possible. A final study developed next generation SABRE methods cascading polarisation from p-H2, via an N-heterocyclic substrate, to platinum-phosphine complexes. Substrates with high polarisation and long lifetimes (e.g., methyl-4,6-d2-nicotinate) proved to be effective for such polarisation relay and resulted in improved 31P signal detection.