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Reference : UMR9012-LAUMEN-002
Workplace : ORSAY,ORSAY
Date of publication : Monday, October 05, 2020
Scientific Responsible name : Laurent MENARD
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 14 December 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Molecular radiotherapy is currently evolving thanks to the joint development of new tracers and innovative radionuclides, which open the field to a more targeted treatment of cancers. In that context, the large heterogeneity of absorbed doses and the range of effects observed, both in terms of toxicity and response, demonstrate that personalized dosimetry is essential to optimize the administered activity and better define tolerance doses. This relies on the quantification of the biodistribution and kinetics of the radiopharmaceutical at the level of the target and organs-at-risk. In clinical practice, such information is obtained during the planning process from the image of a pre-therapeutic radiotracer or, during treatment, using a counting probe. However, the best way to obtain a true quantification of the absorbed dose would be to make an image of the distribution and biokinetics of the radionuclide during treatment, which is not possible with conventional devices, due both to their performance (high activity, high energy gamma rays), ergonomics and availability (in order to access an accurate temporal sampling of the radiotracer kinetics).
This thesis proposal is part of the THIDOS project (Optimization of the individualized patient dosimetry in radioiodine therapy of thyroid diseases) whose objective is to propose new instrumental and methodological approaches aiming to strengthen the control of the dose delivered during radioiodine therapy of thyroid diseases by reducing the uncertainties associated to dose calculation. This project is mainly based on the development of a high spatial resolution mobile gamma camera specifically designed to quantitatively measure at the patient's bedside the biokinetics of 131I in the thyroid and organs at risk (salivary glands) before and after treatment administration. The second axis focuses on the analysis of the reliability and quality of dose calculations based on the integration of various input data (functional and anatomical, pharmacokinetic), including those provided by the novel high-resolution camera, into computational dosimetry models. A clinical feasibility study, conducted as part of the treatment of differentiated thyroid cancers and benign thyroid diseases, will then aim to demonstrate the contribution of our developments to better correlate the actual dose delivered to the expected one, as well as to the observed clinical effects (destruction of tumor remnants, thyroid function, toxicity on salivary glands). This project is carried out in collaboration between the IJCLab, IRSN (Internal dose assessment laboratory of the Internal Dosimetry Department) and the Claudius Régaud Institute (IUCTO, Toulouse). It is funded by the Cancer Plan (INSERM).
A first feasibility prototype of the ambulatory gamma camera (5x5 cm2 field of view) has been developed on the basis of instrumental solutions already developed at our laboratory (inorganic scintillators and silicon photomultiplier arrays). Its evaluation on phantom sources showed very promising results in line with theoretical estimates. In the continuity of this first feasibility study, the THIDOS project is articulated around four main objectives which constitute the core of the thesis proposal:
1) To develop a new clinical prototype of the mobile camera optimized in terms of field of view (10x10 cm2) and performance (counting rate, sensitivity) to meet the constraints of controlling the dose delivered to the thyroid and organs at risk before and during 131I treatment. Characterize the photodetection module and validate the collimators designed by Monte Carlo simulation.
2) Characterize and calibrate the camera response (spatial/energy resolution and sensitivity) for quantification. Implement and validate correction methods (partial volume effect for small targets or heterogeneous uptakes, diffusion, dead time) using physical and digital 3D phantoms (thyroid phantoms with inserts and specific phantom of salivary glands).
3) Evaluate the accuracy and robustness of the protocol for quantifying the activity in the thyroid and organs-at-risk (correction methods, acquisition time, number of angular views, ...) using 3D phantoms mimicking the treatment of benign thyroid diseases or differentiated thyroid cancers. Compare the performance of the mobile camera to those achieved with conventional systems (planar gamma camera, SPECT, gamma counting probe).
4) To clinically evaluate the dosimetric interest of the camera in the treatment of cancers and benign thyroid diseases.
The ideal candidate will have a background in subatomic or medical physics. He/she should have a strong interest for instrumentation, involving simulation-based design, development and characterization of imaging devices. Skills in dosimetry would be considered positively. More generally, a good background in computed sciences is required. Finally, the multidisciplinary nature of the proposed topic will require rigour and a sense of relationship to interact with the different partners (engineer, radiophysicist, nuclear physician) and to coordinate the actions of the different parts of the project.
The “Laboratoire de Physique des 2 Infinis Irène Joliot-Curie” (Laboratory of the Physics of the two infinities Irène Joliot-Curie) or IJCLab (UMR 9012) is a joint research unit of CNRS, Université de Paris and Université Paris Saclay, located on the Orsay campus. The Physics and Health pole, which brings together around fifteen researchers, is structured around three main areas of research carried out by three teams: preclinical and clinical multi-modal imaging (optical and isotopic), radiotherapy and modeling of living organisms.
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Applications should include a detailed CV and a cover letter.
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