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Optimisation of imaging methods: Cellular dosimetry of the radioactive tracers used in positron emission tomography (PET) imaging

​Marion Jacquemin has defend her thesis on Wednesday 7th october 2020 at Fontenay-aux-Roses (France)​

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Authors > JACQUEMIN Manon

Publication Date > 07/10/2020


​In vitro labelling of cells with β+-emitting radionuclides combined with nuclear medicine imaging is a potential method for in vivo cell trafficking analysis with PET imaging. The labeling-associated exposition of cells to high levels of activity still raises some concerns since it may result in cell death and therefore a loss of image quality. In addition, the administration of potentially damaged cells rises essential questions regarding the safety of such procedure.
This research work was conducted with a view of better understand the issues underlying the radiolabelling procedure in order to optimize the current clinical practice. More precisely, this thesis focused on the calculation of the absorbed doses to cells during in vitro 18F-FDG radiolabelling and the correlation to the biological observed effects.
As a first step, computing tools at the multi-cellular scale were developed and optimized. Based on a generic approach which applied to all types of radionuclides or cellular configurations, we explored and compared several hybrid methods mixing Monte Carlo simulations, analytic approaches or molecular dynamics. Then, JURKAT and adipose mesenchymal stem cells (adMSCs) were radiolabelled with 18F-FDG and tested for clonogenic survival assay, cell cycle analysis and γ-H2AX phosphorylation quantification. The cell density and incubation time were fixed but the ¹⁸F-FDG added activity was changed, such as the total absorbed dose to cells resulted in the ranges 0-4 Gy for JURKAT and 0-10 Gy for adMSCs. To this end, we developed a multi-cellular dosimetry model describing the full experiment, from the incubation of cells with ¹⁸F-FDG, washing steps, to culture of cells for functional assays. Dynamic changes in cell density, as well as experimentally determined activity uptake and retention with time were thus considered. Lastly, the mean cell absorbed dose was correlated with the three biological endpoints and results were compared with X-ray irradiation (2.5 Gy/min). The results helped to better undertand the irradiation features associated to 18F-FDG labelling and the observed biological effects, thus providing a knowledge base in favour of harmonizing the labelling methods.

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