Targeted radiotherapy (TRT) is a technique which allows for individual cancer cells to be targeted by radiation. However, there is variation in uptake at the whole body, organ, cellular and subcellular levels. This distribution affects the biological efficacy of the TRT agents. To address this problem, novel techniques have been developed and demonstrated. These aim to provide quantitative information about the spatial distribution of Auger electron (AE) emitting radiopharmaceuticals at the subcellular level. Two methods have been developed. The first, photoresist autoradiography (PAR), uses photoresists as an autoradiography substrate, and the second uses microautoradiography (MAR) and a transmission electron microscope (TEM). The techniques have been demonstrated using the AE emitter indium-111. Firstly, PAR is demonstrated using poly (methyl methacrylate) (PMMA). Photoresists were exposed to indium-111 which had been internalised into cells, and the photoresists were analysed using atomic force microscopy (AFM). The technique has a theoretical resolution in the nanometre range and was able to demonstrate cellular patterns on the micron scale. To gain quantitative information, the photoresist response (depth of pattern) was calibrated as a function of electron fluence and a model of the patterns was created. Combining the calibration data with the point source model allowed the position and intensity of the internalised source terms to be estimated using the PAR method. Secondly, a technique for electron microscope-microautoradiography (EM-MAR) was developed. The processing conditions of the MAR technique were determined and staining techniques developed, to produce high quality TEM micrographs. A time course experiment showed the distribution and variation in the uptake of the radiopharmaceutical at the cellular level. Both techniques are able to provide information about the subcellular distribution of the radioactivity at a higher resolution than current techniques. Both enable the collection of information which can be used in microdosimetric calculations.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730083 |
| Date | January 2016 |
| Creators | Royle, Georgina |
| Contributors | Falzone, Nadia ; Vallis, Katherine |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:83c94d40-91a2-4175-b208-b5ea1bd5a207 |
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