Evaluation of Lu-177 radiotherapy applications based on Monte Carlo simulations

• Κύριος συγγραφέας: Κλωτσοτύρα, Αικατερίνη
• Άλλοι συγγραφείς: Καγκάδης, Γεώργιος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Lu-177; Μonte Carlo; Καρκίνος; Νευροενδοκρινείς όγκοι

Cancer is very common nowadays and it occurs in many different forms to people of all ages. Neuroendocrine tumors were treated only with somatostatin analogs such as Octreotide LAR since they could not be noticed until a large tumor burden appears, something that makes them difficult to be operated. 177Lu-DOTA-TATE is a radiolabeled somatostatin analog that after the NETTER-1 Trial, gained EMA and FDA approval in order to be used at a type of radionuclide therapy called Peptide Receptor Radionuclide Therapy (PRRT). This radiopharmaceutical delivers toxic radiation to the tumor cells after it is bound to somatostatin receptors that are overexpressed on tumor cells’ surface and causes lethal damage to their DNA. Insufficiency of the kidneys could be a serious side effect of the 177Lu-DOTA-TATE PRRT, as their dose tolerance is up to 23 Gy or 27 Gy in some situations. The estimation of the absorbed dose is critical to ensure that radiation-related side effects are kept to a minimum. The aim of this thesis was to perform two Monte Carlo simulations. The first one was based on the PET/CT image of a patient after the pre-therapeutic 68Ga-DOTA-TOC administration, and the other was based on the SPECT/CT image after the PRRT with 177Lu-DOTA-TATE. The first image is used to predict the theoretical biodistribution of 177Lu-DOTA-TATE as the two radiopharmaceuticals share the same target cells. The expected absorbed dose from the PRRT was calculated from the simulation by replacing 68Ga with 177Lu as the irradiating radionuclide. As a result, a comparison was made between the expected, theoretical absorbed dose and the real absorbed dose, calculated in the second simulation based on the image after the PRRT. Furthermore, tumor-to-kidneys, liver-to-kidneys, and liver-to-bone marrow dose ratios were calculated to compare the absorbed dose for the two radiopharmaceuticals. Monte Carlo simulations were performed using GATE application, and a patient’s CT image was utilized as the model of human anatomy. Manual segmentation was done resulting in the organs that are the radiation sources. The SPECT image after the administration of 177Lu-DOTA-TATE and the PET image of 68Ga-DOTA-TOC reveal the size of the tumor. The evaluation of the absorbed dose to the organs of interest was done with personalized organ sizes. 14 10,100,000,000 primaries were used in the simulations and the statistical uncertainty of the results is up to 3.5%. The results of Monte Carlo simulations indicate that there are differences in the absorbed dose of the two radiopharmaceuticals from 4.49% to 36.68%. The dose ratios for both radiopharmaceuticals, although they are not coinciding as it was expected, they agree with the already published results. Even though the option of Peptide Receptor Radionuclide Therapy with 177Lu-DOTA-TATE is available for some years, there is a standard treatment protocol that distinguishes only different categories of patients. In order to achieve the optimal outcome of the therapy without the risk of severe side effects that affect the quality of life of the patients, patient-specific dosimetry is essential.