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The development of targeted TiO2 nanoparticles for the detection of trastuzumab responsive breast tumours by positron emission tomography

Screening of breast cancer patients for their tumour's prognostic marker status is necessary in determining the most suitable course of treatment. This is particularly important in the assessment of HER-2 expression status in identifying candidates who may respond to trastuzumab therapy. Current methods are limited in their effectiveness in accurately determining actual marker status.Discussed herein is an investigation into the development of a titanium dioxide nanoparticle system which may be applied as a medical imaging methodology through the use of positron emission tomography to gauge accurately a patient's HER-2 expression status in identifying candidates for trastuzumab therapy. The initial synthesis of organically coated ultra-small titanium dioxide nanoparticles is discussed in depth with respect to a range of coating molecules and further functionalisation. Additionally, methodology to elicit an exchange of these coat molecules is explored in detail resulting in the generation of TiO2 nanoparticles capable of forming long-term stable suspensions in water. An exploration of the synthesis of fluoride accepting groups for use in generating radiolabelled compounds is explored both successfully and unsuccessfully leading to the development of conditions suitable for radiolabelling aryltrifluoroborate compounds. Attempts to then combine these radionuclide accepting groups with biologically compatible TiO2 nanoparticles are discussed as an initial step toward the generation of a potential PET tracer. However, while this conjugation was achieved, a successful demonstration of the radiolabelling was not achieved requiring further focus on modulating the nanoparticle to easily allow its recovery from such reactions. Finally, an investigation into the effects of trastuzumab and cetuximab on FDG uptake by cells in vitro is discussed with respect to the potential of monitoring disease response to these drugs with conventional FDG-PET.
Date January 2011
CreatorsCheyne, Richard William
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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