Application of a new spectral deconvolution method for in vitro dosimetry in assessment of targeted alpha therapy

Abstract

AbstractBackgroundThe improvement of in vitro assessment of targeted alpha therapy (reproducibility, comparability of experiments…) requires precise evaluation of the dose delivered to the cells. To answer this need, a previous study proposed an innovative dosimetry method based on α‐spectroscopy and a specific deconvolution process to recover the spatial distribution of 212Pb isotopes inside in vitro culture wells. Nevertheless, although promising, the deconvolution method was time consuming and only tested for a simple isotope decay chain.PurposeThe purpose of this work is to propose a new matrix deconvolution method of α spectra based on a constrained‐non‐negative‐maximum‐likelihood decomposition, both faster and offering a greater modelling flexibility, allowing to study independently the kinetics of each of the daughter nuclides of complex decay chains (illustrated here with 223Ra) in in vitro culture wells.MethodsFirstly, the performance of the new method was fully evaluated through Monte Carlo simulations of in vitro irradiations. Different spatial distributions of 212Pb and 223Ra, the corresponding α spectra measured by a silicon detector and the doses delivered to the cells were simulated with Geant4. The deconvolution results were then compared to the simulation results. Secondly, measurements were carried out in culture wells without cells containing 15 kBq of 212Pb or 9.3 kBq of 223Ra, placed above silicon detectors recording α spectra in real time. The matrix deconvolution was then applied to determine the spatial and temporal distribution of all α‐emitting daughters of studied isotopes.ResultsThe matrix deconvolution was proved to recover the simulated distribution gradients, ensuring simulated doses within 3 % for both tested radionuclides, with errors on dose normally distributed around the reference value (consequently not exhibiting any bias), even in the case of complex decay chains as 223Ra. The experimental study of 212Pb and 223Ra showed highly inhomogeneous distributions and time evolution of the concentration gradients, consistent with the previous study. Furthermore, it highlighted the complex kinetics of 223Ra with different distributions of its α‐emitting daughters (219Rn, 215Po, 215At, 211Bi, 211Po).ConclusionsThis study validates a new deconvolution method, fast and flexible, that proved to be accurate and reliable. This method allowed to reveal the complexity of isotopes kinetics in in vitro experiments, especially with complex decay chains. Experimental dosimetry, necessary to improve reliability of in vitro studies in targeted alpha therapy, is demonstrated to be feasible with the proposed method.