Details of Grant 

EPSRC Reference:	EP/F000170/1
Title:	Fluorinated Paramagnetic Probes for Magnetic Resonance Imaging and Spectroscopy
Principal Investigator:	Parker, Professor D
Other Investigators:	Blamire, Professor AM
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	Durham, University of
Scheme:	Standard Research
Starts:	01 October 2007	Ends:	31 December 2010	Value (£):	107,925
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Co-ordination Chemistry
EPSRC Industrial Sector Classifications:	Healthcare Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 08 May 2007 Chemistry Prioritisation Panel (Science) Announced
Summary on Grant Application Form
Studies of compounds containing fluorine in chemistry and biology are attractive because the 19-F nucleus is very amenable to study by nuclear magnetic resonance (NMR) techniques. Its high NMR sensitivity and large chemical shift range , accompanied by a near-zero background signal in cellulo and in vivo, make 19-F NMR studies intrinsically very attractive. Several reports have described the use of 19-F magnetic resonance spectroscopy to track the fate of 19-F labelled drugs, e.g. the metabolism and pharmacokinetics of the anti-cancer drug 5-fluorouracil. Moreover, several studies have been published defining perfluorinated compounds that may be linked to large biomolecules, allowing the tracking of the conjugate, e.g. monitoring labelled actin or myosin during the polymerisation of actin . Key advantages of NMR reporters over radiolabelled compounds are the long shelf-life, lack of radioactivity and the ability to distinguish between starting compounds and products derived from them. Indeed, using a modern imaging method (chemical shift imaging) the use of frequency selective methods allows only those compounds with a particular chemical shift to be monitored, in a method called chemical shift imaging (CSI).A limiting aspect of these recent CSI studies is that high concentrations are required to observe the fluorinated substrates. This restriction is less of an issue in 19-F spectrosocpy studies. Another critical limiting feature of this work is the slow relaxation time of the 19-F nucleus, especially for trifluoro groups, where relaxation times are of the order of seconds; this limits the number of scans that can be acquired in a given period, owing to the need to wait for a long repetition time. As signal/noise varies with the square root of the number of scans acquired, an order of magnitude increase in the rate of relaxation is required. A solution to this problem is to place the 19-F label close to a paramagnetic lanthanide ion, in a stable macrocyclic complex, leading to much shorter relaxation times for the integral 19-F nucleus to be observed. An obvious analogy is with Gd proton MRI contrast agents, for which related macrocyclic complexes have been used clinically since 1988, in tens of millions of MR scans; they are well tolerated in the body at concentrations of up 0.2 mMkg-1. The lanthanide (Ln) ion will be varied in the new F-labelled complexes, allowing the introduction either of strongly relaxing ions (e.g. dysprosium or terbium) or of Ln ions that cause large dipolar shifts, but do not broaden the observed resonance too much, e.g. ytterbium and europium. Various new paramagnetic lanthanide complexes will be prepared containing one or more 19-F labels, and their utility assessed for spectroscopic and imaging studies evaluated in vitro, inside living cells and ultimately, in vivo. The possibility of using this methodology to track gene expression will also be assessed.
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