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Positron Emission Tomography (PET) is a non-invasive medical imaging technique which allows the bio-distribution and pharmacokinetics of labelled molecules to be determined in vivo. Due to these key advantages over other imaging modalities (e.g. MRI, CT, X-ray) the global demand for PET imaging services has seen significant increases with 1.8 million clinical procedures ($332M) being conducted in 2007, a 21% rise on 2006. This rapid growth is expected to continue long term, as access to PET services increases generally, and particularly outside the US, with 7.1 million annual procedures predicted by 2015. However, it's highly significant to the current proposal that the vast majority (>95%) of this market currently only involves the application of a single imaging agent; [18F]FDG, which is generic, and as such typically only used to detect metabolically active tumours in oncology.This surprising lack of suitable imaging agents is the direct result of current limitations in conventional synthetic radiochemical methods, which place severe restrictions on both the positioning of a fluorine-18 label within individual imaging molecules, and the classes of molecule that can actually be effectively used as imaging agents. Indeed, in most cases multiple steps and multiple pot transformations are required to synthesise suitable tracers, but the very short half-life of fluorine-18 (half-life = 110 min) coupled to the complexity of the requisite methodology, make process automation, pre-clinical to clinical research translation, and therapeutic and/or diagnostic area expansion (e.g. neurology, endocrinology, and cardiology etc) extremely difficult.To meet this burgeoning need researchers at Newcastle University have developed the first generic, efficient, and highly selective approach to the formation of [18F]fluoroarene imaging agents. The process places little or no restriction on the substrate thereby allowing the production of multiple tracer candidates that have been previously unobtainable using traditional synthetic approaches. Moreover, the technology uses a 'one-step-one-pot' process, irrespective of the primary substrate. This is both essential with a view to future process automation and existing technology-fit , and of critical significance from the perspective of end stage GMP grade manufacture.By way of example, 4[18F]SFB is a key imaging agent widely used in pre-clinical research to label peptides and other bio-macromolecules, but to date, is yet to realise its true clinical potential as its production typically involves a laborious and complex 'three-step-three-pot' process. However, using proprietary methodology a 'one-step-one-pot' process for the production of this agent has been developed, and has also provided the only route to 2[18F]SFB and 3[18F]SFB derivatives, allowing further refinement and optimisation of these agents.In summary the technology developed at Newcastle makes possible for the first time, the highly efficient and cost effective preparation of multiple imaging agents, to be used in a diverse range of diagnostic and/or therapeutic applications. Clinical access to such a library not only brings the goals of personalised medicine that much closer, but also goes a considerable distance towards meeting the requirements of clinical, academic and industrial PET researchers globally.
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