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

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Reijonen , V , Kanninen , L K , Hippeläinen , E , Lou , Y-R , Salli , E , Sofiev , A , Malinen , M , Paasonen , T , Yliperttula , M , Kuronen , A & Savolainen , S 2017 , ' Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids ' , Physica Medica , vol. 40 , pp. 72-78 .

Title: Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids
Author: Reijonen, Vappu; Kanninen, Liisa K.; Hippeläinen, Eero; Lou, Yan-Ru; Salli, Eero; Sofiev, Alexey; Malinen, Melina; Paasonen, Timo; Yliperttula, Marjo; Kuronen, Antti; Savolainen, Sauli
Contributor organization: HUS Comprehensive Cancer Center
Department of Oncology
Faculty of Pharmacy
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
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
Date: 2017-08
Language: eng
Number of pages: 7
Belongs to series: Physica Medica
ISSN: 1120-1797
Abstract: 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.
Subject: Dosimetry
Radiation dose-response relationship
217 Medical engineering
114 Physical sciences
318 Medical biotechnology
317 Pharmacy
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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