Abstract

A microdosimetry model was developed for the prediction of cell viability for irregular non-spherical cells that were irradiated by low energy, short range Auger electrons. Measured cell survival rates for LNCaP prostate cancer were compared to the computational results for the radioisotopes 177Lu and 161Tb (conjugated to PSMA). The cell geometries used for the computations were derived directly from the cell culture images. A general computational approach was developed to handle arbitrary cell geometries, based on distance probability distribution functions (PDFs) derived from basic image processing. The radiation calculations were done per coarse grained PDF bin to reduce computation time, rather than on a pixel/voxel basis. The radiation dose point kernels over the full electron spectrum were derived using Monte Carlo simulations for energies below 50 eV to account for the propagation of Auger electrons over length scales at and below a cellular radius. The relative importance of short range Auger electrons were evaluated between the two nuclide types. The microdosimetry results were consistent with the cell viability measurements, and it was found that 161Tb was more efficient than 177Lu primarily due to the short range Auger electrons. We foresee that imaging based microdosimetry can be used to evaluate the relative therapeutic effect between various nuclide candidates.

Highlights

  • The dose distribution in radioimmunotherapy can be controlled by a selection of carrier molecules that have affinity to specific cancer cell receptors, and by choosing specific radionuclides with a characteristic penetration depth of the emitted particles

  • The microdosimetry results were consistent with the cell viability measurements, and it was found that 161Tb was more efficient than 177Lu primarily due to the short range auger electrons

  • Our computations are tailored to handle the non-spherical cell geometry as measured, and this is needed for accurate testing of auger-based radioimmunotherapies

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Summary

June 2021

Teresa L Palmer , Kinga Tkacz-Stachowska, Roar Skartlien, Nasrin Omar, Sindre Hassfjell, Andreas Mjøs, Johannes Bergvoll, Ellen M Brevik and Olaug Hjelstuen. Any further distribution of cells that were irradiated by low energy, short range auger electrons. The cell geometries used for the computations were derived directly and DOI. A general computational approach was developed to handle arbitrary cell geometries, based on distance probability distribution functions (PDFs) derived from basic image processing. The relative importance of short range auger electrons were evaluated between the two nuclide types. The microdosimetry results were consistent with the cell viability measurements, and it was found that 161Tb was more efficient than 177Lu primarily due to the short range auger electrons. We foresee that imaging based microdosimetry can be used to evaluate the relative therapeutic effect between various nuclide candidates

Introduction
Microdosimetry for general cell geometries
Cell line experiments
Image processing and geometry modeling based on 2D images
Cross dose approximations
Microdosimetric results
Findings
Discussion
Conclusion

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