Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids

Autor: Liisa Kanninen, Antti Kuronen, Timo Paasonen, Vappu Reijonen, Yan-Ru Lou, Alexey Sofiev, Melina Malinen, Marjo Yliperttula, Eero Salli, Sauli Savolainen, Eero Hippeläinen
Přispěvatelé: HUS Comprehensive Cancer Center, Department of Oncology, Faculty of Pharmacy, HUS Medical Imaging Center, Department of Diagnostics and Therapeutics, Clinicum, Division of Pharmaceutical Biosciences, Nanobio Pharmaceutics, Drug Research Program, Tissue engineering for drug research, Department of Physics, Sauli Savolainen / Principal Investigator, Helsinki In Vivo Animal Imaging Platform (HAIP), Biopharmaceutics Group
Rok vydání: 2016
Předmět:
SELECTION
Materials science
Carcinoma
Hepatocellular
medicine.medical_treatment
Monte Carlo method
MODELS
Biophysics
SEGMENTATION
General Physics and Astronomy
RADIONUCLIDE THERAPY
Radiation
BIOLOGIC RESPONSE
Radiation Dosage
114 Physical sciences
LEVEL DOSIMETRY
030218 nuclear medicine & medical imaging
03 medical and health sciences
0302 clinical medicine
Dosimetry
Spheroids
Cellular
medicine
NANOFIBRILLAR CELLULOSE
TOOL
Humans
Radiology
Nuclear Medicine and imaging
Radiometry
Absorbed Radiation Dose
318 Medical biotechnology
Radiotherapy Planning
Computer-Assisted
ALGORITHMS
Spheroid
Dose-Response Relationship
Radiation
General Medicine
217 Medical engineering
Hep G2 Cells
Radiation therapy
317 Pharmacy
030220 oncology & carcinogenesis
Absorbed dose
Radionuclide therapy
Radiation dose-response relationship
MONTE-CARLO-SIMULATION
Radiopharmaceuticals
Cell-level
Monte Carlo Method
Biomedical engineering
Zdroj: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB). 40
ISSN: 1724-191X
Popis: Purpose: Absorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals. Methods: A confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain In-111, I-125, or Lu-177. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE. Results: We developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for 177Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with 111In and 125I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared. Conclusions: We computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT. (C) 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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