Monte Carlo dosimetry of a realistic multicellular model of follicular lymphoma in a context of radioimmunotherapy

Abstract

Small-scale dosimetry studies generally consider an artificial environment where the tumors are spherical and the radionuclides are homogeneously biodistributed. However, tumor shapes are irregular and radiopharmaceutical biodistributions are heterogeneous, impacting the energy deposition in targeted radionuclide therapy. To bring realism, we developed a dosimetric methodology based on a three-dimensional in vitro model of follicular lymphoma incubated with rituximab, an anti-CD20 monoclonal antibody used in the treatment of non-Hodgkin lymphomas, which might be combined with a radionuclide. The effects of the realistic geometry and biodistribution on the absorbed dose were highlighted by comparison with literature data. Additionally, to illustrate the possibilities of this methodology, the effect of different radionuclides on the absorbed dose distribution delivered to the in vitro tumor were compared. Methods: The starting point was a model named multicellular aggregates of lymphoma cells (MALC). Three MALCs of different dimensions and their rituximab biodistribution were considered. Geometry, antibody location and concentration were extracted from selective plane illumination microscopy. Assuming antibody radiolabeling with Auger electron (125 I and 111 In) and β − particle emitters (177 Lu, 131 I and 90 Y), we simulated energy deposition in MALCs using two Monte Carlo codes: Geant4-DNA with "CPA100" physics models for Auger electron emitters and Geant4 with "Livermore" physics models for β − particle emitters. Results: MALCs had ellipsoid-like shapes with major radii, r, of~0.25,~0.5 and~1.3 mm. Rituximab was concentrated in the periphery of the MALCs. The absorbed doses delivered by 177 Lu, 131 I and 90 Y in MALCs were compared with literature data for spheres with two types of homogeneous biodistributions (on the surface or throughout the volume). Compared to the MALCs, the mean absorbed doses delivered in spheres with surface biodistributions were between 18% and 38% lower, while with volume biodistribution they were between 15% and 29% higher. Regarding the radionuclides comparison, the relationship between MALC dimensions, rituximab biodistribution and

Tumor Control Probability and Small-Scale Monte Carlo Dosimetry: Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy

“…In addition, the targeted epitopes of the tumor cells might not be equally available because of restricted tumor penetration or varying expression. Bordes et al (25) used the measured uptake of rituximab by fluorescence microscopy in a multicellular aggregate of lymphoma cells, distinctly limited to the edges, to represent activity uptake in Monte Carlo simulations of the absorbed dose rate per activity unit in multicellular volumes (25). This method is favored by the greater resolution of fluorescence microscopy.…”

A GATE simulation study for dosimetry in cancer cell and micrometastasis from the 225Ac decay chain

“…The calculations of cellular S-values by MIRD are based on convolution integrals, a semi-analytic method which applies the continuous slowing down approximation (CSDA). To address the limitations of the CSDA methodology, Monte Carlo track-structure (MCTS) methods have been studied to evaluate a number of radionuclides at a cellular level via simulations of radiation transport [18,[20][21][22][23][24][25][26][27][28][29]. However, in most studies, the focus has been largely on beta-emitting radionuclides with simple decay schemes, while a limited number of dosimetry studies focused on alpha emitters or 225 Ac, specifically [22,30,31].…”

Small-scale dosimetry for alpha particle 241Am source cell irradiation and estimation of γ-H2AX foci distribution in prostate cancer cell line PC3

“…Consequently, the absorbed dose, or in microdosimetric terms, the specific energy [ 10 ], in the cells or cell nuclei has a high variability [ 11 ]. Similarly, intratumoral variation of dosimetric quantities is to be expected in tumors with uptake heterogeneities for radiopharmaceuticals emitting radiation of short range [ 12 ]. In this aspect, uncollimated source irradiations to some degree mimic the complex in vivo dosimetric case, but is less complex to perform in comparison with the addition of a radiopharmaceutical to the culture media, where the uptake and internalization need to be quantified to build a robust dosimetry model.…”