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Title: Zirconium-89 complexes for cell tracking with positron emission tomography
Author: Ferris, Trevor John
ISNI:       0000 0004 5364 0853
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2015
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Tracking cell migration in vivo by scintigraphy using cells labelled with gamma-emitting radionuclides (especially indium-111) is a well-established clinical and research tool. Positron emission tomography offers improved sensitivity and resolution, but there are no established cell labelling methods using suitable long-lived isotopes. The long half-life positron emitter zirconium-89 (half-life 78.4 h) is a strong candidate for cell labelling and cell tracking, and is becoming increasingly available. It has no known biological role or transport mechanisms. The aim of this research was to produce a range of candidate neutral zirconium L4 lipophilic complexes that could be prepared under radiopharmaceutical conditions and used in cell labelling. This aim was achieved with the ligands; oxine, tropolone and ethyl maltol. The resulting complexes can be prepared in high yield from zirconium precursors in hydrochloric or oxalic acid solution. A deferiprone complex was prepared from deferiprone and zirconium tetrachloride, but was found to lack lipophilic properties and it was not possible to prepare the deferiprone complex under radiopharmaceutical conditions. Analytical techniques such as carbon, hydrogen and nitrogen elemental analysis, nuclear magnetic resonance spectroscopy, fourier transform infrared spectroscopy, and Raman spectroscopy have been used to characterise the complexes. The oxine and tropolone complexes were the most amenable to chromatographic characterisation and high performance liquid chromatography and instant thin layer chromatography protocols have been established to monitor radiochemical purity. Cell uptake and efflux of zirconium-89 tetrakisoxine, tropolone and ethyl maltol utilising the following cell lines was determined; HCT116: colon cancer, J774: mouse macrophage and MDA-MB-231: breast cancer. Zirconium-89 tetrakisoxine has emerged as a lead compound. Zirconium-89 tetrakisoxine labelled myeloma cells retained the radiotracer in vivo for up to 7 days. Zirconium-89 tetrakisoxine was found to be a promising cell tracking agent for long term cell tracking studies.
Supervisor: Went, Michael; Blower, Philip Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available