Realistic multi-cellular dosimetry for 177 Lu-labelled antibodies: model and application

Autor: Sara Marcatili, Riad Ladjohounlou, Helen Heyerdahl, Jostein Dahle, Alexandre Pichard, Isabelle Navarro-Teulon, A. Courteau, Manuel Bardiès, Jean-Pierre Pouget, Ada H. V. Repetto-Llamazares
Přispěvatelé: Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Radiobiology
medicine.medical_treatment
Monte Carlo method
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH: Monte Carlo Method
030218 nuclear medicine & medical imaging
03 medical and health sciences
3D cell culture
MESH: Software
0302 clinical medicine
MESH: Lymphoma
Non-Hodgkin

medicine
Dosimetry
Radiology
Nuclear Medicine and imaging

MESH: Tumor Cells
Cultured

MESH: Tissue Distribution
Clonogenic assay
Physics
MESH: Humans
Radiological and Ultrasound Technology
business.industry
MESH: Models
Biological

MESH: Radiometry
3. Good health
Radiation therapy
030220 oncology & carcinogenesis
Absorbed dose
MESH: Antineoplastic Agents
MESH: Rituximab
Cellular model
Biological system
Nuclear medicine
business
MESH: Lutetium
MESH: Radiopharmaceuticals
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Physics in Medicine and Biology
Physics in Medicine and Biology, IOP Publishing, 2016, 61 (19), pp.6935-6952. ⟨10.1088/0031-9155/61/19/6935⟩
ISSN: 0031-9155
1361-6560
DOI: 10.1088/0031-9155/61/19/6935⟩
Popis: International audience; Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.
Databáze: OpenAIRE