Dr PETER HARVEY PETER.HARVEY@NOTTINGHAM.AC.UK
Associate Professor
Novel paramagnetic lanthanide complexes have been synthesised for use as probes for magnetic resonance imaging and spectroscopy. Initially, complexes containing a trifluoromethyl group were examined for 19F MRI/S, due to the large chemical shift range, favourable NMR properties, and the absence of a background signal in vivo. The use of paramagnetic lanthanide ions increases relaxation rates, allowing faster acquisition times and increased signal intensity per unit time. In addition, chemical shift non-equivalence is enhanced, which is important for the development of responsive probes. Examples are presented that report selectively on changes to citrate concentration levels in the presence of other anions or signal enzyme hydrolysis.
To improve signal intensity for in vivo applications, conjugate systems have been developed containing a number of fluorinated lanthanide complexes covalently bound to high molecular weight adducts (glycol chitosan, PAMAM dendrimer). These systems resulted in one major species being observed in solution, despite the broad molecular weight ranges exhibited by these polymeric entities. Preliminary in vivo MRI studies in animal models were undertaken with the glycol chitosan conjugate.
In order to enhance the signal further, a set of fluorinated complexes was synthesised containing a pyridyl moiety designed to increase the rigidity of the overall system, thereby reducing dynamic exchange broadening. Additionally, the 19F NMR spectra of these complexes displayed much larger lanthanide induced shifts than observed for the previous systems. By substituting the CF3 group for a tert-butyl moiety, the corresponding 1H NMR signal was shifted well beyond the standard diamagnetic range, leading to the development of a new series of complexes for use as 1H MRI and MRS probes. These complexes have been applied to preliminary in vivo MRI studies. A further system has been developed that displays pH-dependent behaviour, observed by both 1H NMR spectroscopy and in phantom imaging studies.
Harvey, P. Paramagnetic Probes for Magnetic Resonance. (Thesis). Durham University. Retrieved from https://nottingham-repository.worktribe.com/output/2829768
Thesis Type | Thesis |
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Deposit Date | Oct 24, 2019 |
Publicly Available Date | Apr 3, 2020 |
Keywords | lanthanide; MRI; fluorine; contrast agent |
Public URL | https://nottingham-repository.worktribe.com/output/2829768 |
Award Date | 2013-06 |
Peter Harvey Thesis
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