In vitro dosimetry for assessment of targeted alpha therapy

by Alexis Doudard

Targeted-Radionuclide-Therapy (TRT) is a cancer treatment method based on the use of radio-labeled molecules showing both interesting properties of specific binding to lesions and short range ionizing ray emissions. For the latter matter, alpha particle emitters are of particular interest, their range in biological matter covering only a few cell diameters. One part of new TRT radiopharmaceuticals assessment are in vitro assays, where biological effects on cells are observed and compared to the dose delivered. However, when alpha emitters are involved, the dose delivered is significantly dependent on the spatial distribution of the radionuclides in the culture medium.

We developed a dosimetry setup based on alpha spectroscopy of the in vitro culture wells using silicon semi-conductors. The measured alpha spectra are also dependent on the spatial distribution of the radionuclides. We proposed a spectral deconvolution methodology based on a modified non-negative least squares algorithm. For each acquired spectrum, the extrapolated spatial distribution of the radionuclides allows for computation of the delivered dose through GEANT4 Monte-Carlo simulations. Assessment of our methodology with simulated in vitro assays showed that the whole methodology doesn’t show significant bias, that we could expect errors below 3 %, and that the uncertainty computation reliably covers the true error. We finally present an application of our methodology on spectra acquired with ²²³Ra, and discuss the relevance of additional sources of uncertainties.uclide-Therapy (TRT) is a cancer treatment method based on the use of radio-labeled molecules showing both interesting properties of specific binding to lesions and short range ionizing ray emissions. For the latter matter, alpha particle emitters are of particular interest, their range in biological matter covering only a few cell diameters. One part of new TRT radiopharmaceuticals assessment are in vitro assays, where biological effects on cells are observed and compared to the dose delivered. However, when alpha emitters are involved, the dose delivered is significantly dependent on the spatial distribution of the radionuclides in the culture medium.