Clinical dosimetry in Molecular Radiotherapy

Gunjan Kayal, Lara Struelens

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Abstract

Molecular radiotherapy (MRT) is a systemic radiotherapy where the radiopharmaceutical binds specifically to tumours to selectively kill cancer targets while sparing healthy organs. Lutathera® (177Lu-DOTATATE) is a recently FDA/EMA approved radiopharmaceutical for the treatment of the GastroEnteroPancreatic NeuroEndocrine Tumours (GEP-NETs). In clinical practice, patients are administered with a fixed activity of Lutathera®,
assuming that radiopharmaceutical distribution is the same for all patients. Patientspecific dosimetry allows for a major paradigm shift in the administration of MRT from “one-size-fits-all” approach, to “real personalised medicine” where administered activity is assessed specifically on the base of the irradiation delivered to each patient. This usually requires determining the spatial distribution of the radiopharmaceutical in various organs via imaging at different times (quantitative imaging), estimating the total number of radioactive decays by integrating activity over time (pharmacokinetic assessment) and calculating the absorbed dose using the physical characteristics of the radionuclide and implementing radiation transport in patient’s tissues.
Currently, there are no standardised procedures to perform clinical dosimetry. In addition, the assessment of the uncertainties associated with the dosimetry procedure is not trivial. The DosiTest project (http://www.dositest.org/) was initiated to evaluate uncertainties associated with each of the steps of the clinical dosimetry workflow, via a multicentric inter-comparison based on Monte Carlo (MC) modelling.
The first phase of the thesis compared dosimetry analysis performed by various centres using the same software and protocol on the same patient dataset as a part of IAEA-CRP E23005 project in order to appraise the precision of clinical dosimetry. To our knowledge, this is the first time that a multi-centric dosimetry comparison of a single clinical patient dataset has been undertaken using the same protocol and software by many centres worldwide. It highlighted the critical need to establish checkpoints and conduct sanity checks to eliminate significant disparities among results, and distinguish erroneous practice with acceptable inter-operator variability. A significant outcome of this work was the lack of quality assurance in clinical nuclear medicine dosimetry and the need for the development of quality control procedures. While dosimetry is gaining popularity in nuclear medicine, best practices should be adopted to ensure that results are reliable, traceable, and reproducible. It also brings forward the need to deliver sufficient training after the acquisition of the relatively new software packages beyond a couple of days. This is clearly insufficient in a context of an emerging field where the professional experience is quite often lacking. Next, the study of clinical dosimetry accuracy requires generating test datasets, to define the ground truth against which clinical dosimetry procedures can be benchmarked. The second section of the thesis addressed the simulation of threedimensional scintigraphic SPECT imaging by implementing auto-contouring detector motion in the GATE Monte Carlo toolkit. Following the validation of SPECT/CT projections on anthropomorphic models, a series of realistic clinical patient images were generated.
The last part of the thesis established the proof of concept of the DosiTest project, using a virtual (simulated) SPECT/CT dataset at various time points, with various gamma cameras, enabling comparison of various dosimetric techniques and to assess the clinical feasibility of the project in selected nuclear medicine departments.
Original languageEnglish
QualificationDoctor of Science
Awarding Institution
  • Université Toulouse III - Paul Sabatier
Supervisors/Advisors
  • Struelens, Lara, SCK CEN Mentor
  • Bardiès, Manuel, Supervisor, External person
  • Chauvin, Maxime, Supervisor, External person
Date of Award31 Mar 2022
StatePublished - 31 Mar 2022

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