Organisation/Company: GANIL
Research Field: Physics » Metrology; Medical sciences » Other
Researcher Profile: First Stage Researcher (R1)
Positions: PhD Positions
Country: France
Application Deadline: 23 May 2025 - 23:59 (Europe/Paris)
Type of Contract: Temporary
Job Status: Full-time
Is the job funded through the EU Research Framework Programme? Not funded by a EU programme
Is the Job related to staff position within a Research Infrastructure? No
Offer Description
Targeted alpha therapy (TAT) is a treatment modality in which a labelled a-emitting radioisotope is injected into the patient. The labelled molecules specifically target tumour cell biomarkers. As a result, the dose deposition produced by the decay of the radioisotopes is concentrated in close proximity to the tumour cells, especially in the case of a-emitters. The favourable properties of a-particles (short range, high linear energy transfer, potent cytotoxicity) explain the increasing development and use of TAT.
Like any new treatment, TAT requires preclinical studies to evaluate the efficacy of new molecules and to compare results with other existing modalities. In vitro experiments are part of this research. They consist of exposing cells cultured in a dish to labelled radioisotopes diluted in culture medium. In this type of experiment, biological effects (such as survival rate) are usually correlated with the injected activity. Although this may be relevant for ß-emitters, it is not for the quantitative assessment of a-emitting radioisotopes. Moreover, to compare the efficiency of TAT with other treatments, knowledge of the absorbed dose in cells is much more relevant.
An innovative method was successfully developed and tested during a preclinical evaluation of 212Pb-VCAM-1 to provide reliable and accurate dose measurements during in vitro experiments. This method is mainly based on the measurement of the energy spectrum of a-particles emitted from the culture medium through a 2.5 µm Mylar wall using silicon detectors and a deconvolution method based on Monte Carlo simulations.
This method has been shown to improve the determination of the spatial and temporal distribution of radioisotopes in in vitro experiments. However, the precise and accurate quantification of the biological effect of alpha particle irradiation requires further investigations and development, particularly regarding the cell geometry model which can strongly influence the fraction of energy absorbed by the cells.
The first part of this thesis will therefore deal with the modelling of cells in in vitro configurations. This study will require the acquisition of cell images and/or the use of existing images. It will then be necessary to determine a relevant geometry to be implemented in the simulations, the variability of this geometry and the impact of this variability in terms of absorbed dose.
The second part of the PhD thesis will concern the evolution of the detection system. The current detection system provides a dose averaged over the whole culture well. For alpha particles, especially for low activities, it may be necessary to obtain a high resolution 2D spatial distribution at the cell level to observe stochastic dose deposition mechanisms. A new detection system based on the use of a scintillator coupled to a microscopic imaging system will be developed and investigated.
Finally, the use of different commercially available scintillators and imaging systems will be compared and optimized to find the best match in terms of scintillation and detection efficiency. Monte Carlo simulations will also be performed to optimize the setup configuration. A prototype will then be implemented and characterized with alpha emitting sources.
This project will be done at GANIL, in the frame of its research program on the production and dosimetry of innovative medical radioisotopes. GANIL has also important skills in nuclear instrumentation and preclinical dosimetry and has developed collaborations with other laboratories (ISTCT, CLCC François Baclesse, Cyceron, LPC Caen…) in interdisciplinary domains.
Where to apply
E-mail: ******
Requirements
Research Field: Physics
Education Level: Master Degree or equivalent
Skills/Qualifications
The student must have an education in nuclear physics with a good knowledge of the detection of radiations and their interactions with matter. Knowledge in radiotherapy and dosimetry would be a plus.
The student will participate in the prototype implementation, perform experimental characterizations and evaluations, as well as Monte Carlo simulations and data analysis.
The candidate must have an interest in experimentation as well as simulation and will need to develop skills in instrumentation, programming, and Monte Carlo simulations.
The candidate should be able to work in an interdisciplinary domain with people from other research fields such as biology, medical physics, or medicine.
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