Optimisation of radiolabelling methodologies for lymphocyte tracking by PET imaging

Almutairi, Hanan 2024. Optimisation of radiolabelling methodologies for lymphocyte tracking by PET imaging. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Cell tracking and labelling have become rapidly growing areas of research in clinical practice, particularly in the context of monitoring and evaluating immune cells and cell-based therapies. In order to effectively implement these therapies in the clinic, it is essential to have a comprehensive understanding of how cells behave and distribute within the body postadministration. The two main preclinically evaluated 89Zr-tracers that have been applied for direct cell labelling are 89Zr-DFO-NCS for cell surface labelling and 89Zr-oxine for intracellular labelling. Although numerous publications have addressed the labelling of cells with 89Zr-oxine and 89Zr-DFO-NCS, direct comparisons between these two cell labelling methods remain limited. A study conducted in 2021 by Friberger et al., provides an insightful in vitro comparison of thes methodologies. In addition, further research by Friberger et al., in 2023 expands upon this comparison by investigating the efficacy of these two labelling techniques in vivo. Therefore, the primary objective of this project was to optimise direct in vitro labelling of lymphocytes with 89Zr complexes, specifically 89Zr-oxine and 89Zr-DFO-NCS, allowing for in vivo tracking of radiolabelled cells via PET/CT imaging in a mouse model using these two compounds simultaneously. In particular, the thesis addressed the following objectives. Chapter 1 provided a general background and an introduction to the topic. Chapter 2 described the methods and materials used in the research project. Chapter 3 discussed the initial attempts to label donor lymphocytes with 89Zr-oxine and 89Zr-DFO-NCS complexes and track the labelled cells in vivo by PET/CT imaging in a mouse model in part 1. Part 2: presented the development of the labelling method for 89Zr-oxine and EL4 cells for in vivo PET imaging. Chapter 4 presented the optimised parameters established from the labelling of EL4 cells to perform in vitro radiolabelling for the in vivo tracking of CTLL2 cells via PET/CT imaging in a mouse model. Finally, Chapter 5 summarised the study, highlighted any limitations 2 encountered, and presents suggestions for future work. We have shown that both 89Zr-oxine and 89Zr-DFO-NCS were successful in labelling T cells and tracking the movement and distribution of the labelled cells in mice using PET/CT imaging.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	26 February 2024
Last Modified:	26 Feb 2024 13:57
URI:	https://orca.cardiff.ac.uk/id/eprint/166545

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