In vitro dosimetry for assessment of Targeted-AlphaTherapy

by Alexis Doudard, 3rd year PhD student at GANIL

Targeted alpha therapy (TAT) is a potent internal radiotherapy of interest for the treatment of small and diffuse targets, such as brain metastases [1][2]. This therapy is based on alpha-emitting radionuclides with decay schemes convenient for clinical use, such as the actinides ²²⁵Ac and  ²²⁷Th [3]. Developments of new TAT treatments include in vitro assays, where their biological effectiveness on tumor cells is compared to other reference treatments through imaging and dosimetry. However, while the short and dense ionization tracks in biological matter of alpha-emissions constitute the main interest of TAT, this property makes in vitro dosimetry heavily dependent on the spatial distribution of the radionuclides in the culture medium [4]. Measurement of this distribution is thus mandatory to back dose-effect relationship assessments and would improve reliability of comparisons with other treatment methods.

We developed an in vitro dosimetry system, which can be used in a cell culture incubator, based on silicon semiconductor detectors recording energy spectra of the alpha-particles emitted within the culture wells and passing through the cell layer. A new spectral deconvolution method of the recorded energy spectra was developed and enables recovery of the spatial and time distributions of the radionuclides during the experiment. This method relies on a database made of pre-computed GEANT4 simulations and is fast enough to allow on-line dosimetry of the assays.

A validation applied to ²¹²Pb and ²²³Ra through simulation of in vitro irradiations demonstrated dose errors due to uncertainties on the computed spatial distribution being limited to 3%. The new experimental system and algorithm were employed in preliminary experiments with ²¹²Pb and ²²³Ra and showed that the spatial distribution of radionuclides is sensitive to the experimental conditions. They also revealed that the different radionuclides of complex decay chains, such as ²²³Ra, may present largely different spatial and temporal distributions, which has further consequences on the dose computation. All these results demonstrated the need for a radionuclide spatial distribution assessment to avoid significant dose misestimations and thus to improve the reliability of conclusions drawn from in vitro assays of TAT.

REFERENCES

[1] N. Falzone et al., Theranostics. 8, 292–303 (2018).
[2] A. Corroyer-Dulmont et al., Neuro-Oncology. 22, 357–368 (2020).
[3] B. J. B. Nelson, J. D. Andersson, F. Wuest, Pharmaceutics. 13, 49 (2020).
[3] R. Eychenne, M. Chérel, F. Haddad, F. Guérard, J.-F. Gestin, Pharmaceutics. 13, 906 (2021).
[4] A. Frelin‐Labalme et al., Med. Phys. 47, 1317–1326 (2020).