Session Item

Recent developments in heavy ions production increased access to alpha-emitting radioisotopes and opened the door to their use in internal radiotherapy[1]. Targeted alpha therapy is of interest for dedicated applications such as the treatment of disseminated and small brain metastases[2][3], their radiation range in biological matter covering only a few dozens of micrometers. However, when alpha-emitting radionuclides undergo in vitro experiments, additional care must be taken compared to beta-emitters because of the higher linear energy transfer values of alpha particles. Indeed, the dose delivered to the cells becomes significantly dependent on the spatial distribution of the radionuclides in the culture medium[4]. Knowledge of this distribution would thus allow dose-effect relationships assessments and make comparisons to other irradiation methods more reliable.

We present here an in vitro dosimetry system using silicon semiconductor diodes placed below custom-made culture wells, which record energy spectra of the alpha particles passing through the culture medium and cell layer during the irradiation. A detector chamber protecting the electronics was designed to carry out the measurements inside a cell culture incubator. A new spectral deconvolution method was developed to extrapolate the radionuclide spatial distribution from energy spectra acquired during in vitro experiments and compute on-line the dose delivered to the cells. Since our custom-made wells are compatible with microscopy imaging, dose-relationship effects can be directly evaluated for all culture wells between actual dosimetry and DNA damage.

Reliability of the spectral analysis methodology has been assessed and demonstrated dose computation errors limited to 3% when applied to simulated 212Pb in vitro irradiations. Applications of this methodology carried out in preliminary experiments using the dedicated spectroscopic setup with 212Pb and 223Ra showed that the common homogenous distribution hypothesis is erroneous and could lead to up to 50% dose underestimation. They also revealed that the different radionuclides of complex decay chains present different spatial and temporal distributions, which has further consequences on the dose computation and highlights the necessity of new experimental dosimetry methods.

Dosimetry through α-spectroscopy, when coupled with a new, fast, and flexible deconvolution method, proved to be accurate and reliable for in vitro assays. More than feasible, experimental dosimetry appears necessary to improve the reliability of the assessment of new targeted alpha therapy radiopharmaceuticals.

REFERENCES
[1] F. Guerard et al., Q J Nucl. Med. Mol. Im. 59, 161-7 (2015)
[2] A. Corroyer-Dulmont et al., Neuro-Oncology 22(3), 357-68 (2020)
[3] N. Falzone et al., Theranostics 8(1), 292-303 (2018).
[4] A.M. Frelin-Labalme et al., Med. Phys. 47(3), 1317-26 (2020)

This project has received financial support from the CNRS through the MITI interdisciplinary programs.