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Radiopharmaceutical dosimetry in targeted radionuclide therapy

Abstract : Nuclear medicine is a medical specialty in which one of whose applications is the study of the physiology of organs and the metabolism of various types of tumours. Pharmaceuticals labelled with radionuclides (radiopharmaceuticals) are studied at pre-clinical level before being used in humans. Rodents are generally used to study the biokinetics of tracer in a group of predefined organs. The extrapolation of the results of these studies from animals to humans provides an estimate of the behaviour of the radiopharmaceuticals and the irradiation delivered clinically. Three new radiopharmaceuticals were developed, one in France (CHU-Hôpital Purpan) and two in Uruguay (CUDIM). Two aim to study the brain and one aims to diagnose prostate cancer. In this work, extrapolation of pharmacokinetics preclinical results to the human is presented; absorbed and effective doses are estimated using OLINDA/EXM V1.0, V2.0 and IDAC2.1 software. The differences between the results of each program are discussed. At a clinical level, dosimetric protocols include calibration factor determination, segmentation, registration, curve fitting, and calculation of absorbed dose. In this work, the calibration developed for a SPECT/CT is presented using different calibration sources and different geometries. The influence of the reconstruction method in the determination of the calibration factor and the recovery coefficient curves are shown. In addition, four commercial software are compared based-on clinical information of two patients with gastro-entero-pancreatic tumours of neuroendocrine origin treated with 177Lu-DOTATATE. Two cycles of treatment for each patient were used to estimate residence times for the kidneys, liver, spleen, bone marrow and whole body. Calculation of absorbed dose was initially developed using OLINDA/EXM V1.0 & V2.0, adjusting the mass of each organ/tissue. In the case of the bone marrow, a novel methodology is presented to estimate the absorbed dose without the need for whole-body measurements. It can be seen that the registration of the images has an impact on the determination of the absorbed dose. The results are thus calculated by employing a tool allowing to register independently each organ and not all the image of the field of view. Different calculation algorithms were used to determine the absorbed dose delivered to patients, for example the OLINDA/EXM V2.0 sphere model, convolution and local energy deposition methods of PLANET®Onco Dose from Dosisoft. The results found with the different tools are compared and discussed.
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Erick Mora Ramirez. Radiopharmaceutical dosimetry in targeted radionuclide therapy. Medical Imaging. Université Paul Sabatier - Toulouse III, 2019. English. ⟨NNT : 2019TOU30012⟩. ⟨tel-02945980⟩

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