Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.681778
Title: 1H parashift probes for magnetic resonance
Author: Finney, Katie-Louise Natasha Aman
ISNI:       0000 0004 5921 5604
Awarding Body: Durham University
Current Institution: Durham University
Date of Award: 2016
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Abstract:
The strong 1H NMR signals from water and fat impose significant limitations to magnetic resonance spectroscopic imaging in vivo. Herein, novel paramagnetic lanthanide probes for 1H magnetic resonance imaging and spectroscopy studies are described, in which a tert-butyl reporter group is incorporated and placed about 6 to 7 Å from a lanthanide(III) ion in a kinetically stable macrocyclic complex. At such a distance, the tert-butyl reporter is shifted to a 1H NMR window that is well removed from the diamagnetic range, allowing its selective observation. Additionally, prudent selection of the lanthanide(III) ion, in accord with magnetic field strength, leads to an enhancement in the longitudinal relaxation rates, R1, permitting faster data acquisition per unit time in spectroscopy and imaging protocols. Further sensitivity gains are achieved by selecting a tert-butyl reporter group, within which the number of magnetically equivalent nuclei is maximised. As a result, the development of 1H PARASHIFT probes with carboxylate chelating arms possess tert-butyl groups that are shifted up to 25 ppm away from the water signal. At such frequencies, the enhanced sensitivity associated with the zero-background signal in vivo, allows the detection of these complexes in live mice, and due to the achievement of the required R1 values, data acquisition occurs within a few minutes following tail vein injection of well-tolerated doses that are of the same size as clinically administered contrast agents (0.1 mmol kg-1). Remarkable tert-butyl chemical shift enhancements up to 85 ppm away from the water signal are observed for 1H PARASHIFT probes possessing phosphinate chelating arms, moving the goal posts further still for 1H MRS studies. Such a shift magnitude means that larger spectral imaging bandwidths (such as 20 kHz) can be used, to further reduce data acquisition times. Minimal structural modifications, in the 4-position of the coordinated pyridyl moiety, have led to the development of ‘smart’ pH responsive 1H PARASHIFT probes, and also a covalently bound high-molecular weight glycol chitosan adduct. In the latter case, a strategy for increasing the retention time of these complexes is presented.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.681778  DOI: Not available
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