18F-FDG Labelling in Cell-Tracking PET Studies: Calculation of the Precise Absorbed Dose Deposited to Cell Nucleus and Correlation to in Vitro Biological Effects
Résumé
Purpose: To investigate the biological impact of in vitro ¹8F-FDG cell labelling with respect to the absorbed dose.
Methods: JURKAT and adipose mesenchymal stem cells (adMSCs) were radiolabelled with 18F-FDG and then tested for clonogenic survival assay, cell cycle analysis and ?-H2AX phosphorylation quantification. The cell density and incubation time were fixed while 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. Calculation of the self, cross and culture medium absorbed doses to the cell nucleus were done using MCNP6 simulations and analytical approaches. 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).
Results: The dose rate calculated over time was found to vary considerably along the labelling procedure. The centrifugation step required for cell washing induced an increase of the dose rate by a factor of 8 (reaching 0.12 Gy/min) and was mostly due to cross-irradiation.
We observed that the survival percentage of cells dropped below 1% from 4.3 Gy and 8.3 Gy for JURKAT and adMSCs, respectively. The range of doses found in the literature for ¹8F-FDG labelling (0.5 Gy up to beyond 20 Gy) suggests that most of administered cells could eventually die, for some cases probably in the course of imaging.
Conclusion: Our dosimetric model allowed to accurately determine the cell dose deposited throughout the ¹8F-FDG labelling. This will help to better understand the observed biological effects.