Microdosimetry aspects in diffusing alpha-emitters radiation therapy: I. Effect of broad nucleus size distributions

Area of Science:

• Radiation Oncology
• Medical Physics
• Radiobiology

Background:

• Alpha DaRT is an emerging treatment for solid tumors using alpha particles.
• Accurate tumor dosimetry is essential for predicting biological responses like cell survival and tumor control probability.
• Microscopic scale dosimetry requires detailed modeling of cellular and nuclear characteristics.

Purpose of the Study:

• To develop a microdosimetric model linking alpha dose, cell survival, and tumor control probability.
• To explicitly account for variations in spherical cell nucleus radii in the model.
• To assess the impact of nucleus size distribution on treatment outcome predictions.

Main Methods:

• Developed a microdosimetric model combining analytic nucleus-hit statistics with Monte Carlo simulations.
• Computed cell survival probabilities using nucleus radii sampled from artificial and empirical distributions.
• Investigated the effect of nucleus size distribution width and minimum size on survival curves.

Main Results:

• Finite nucleus size distributions cause survival curves to deviate from exponential trends, especially at high doses.
• The width of nucleus size distribution significantly affects the survival difference between radiosensitive and radioresistant cells.
• Tumor control probability is highly sensitive to the minimum nucleus size considered, necessitating realistic lower thresholds.

Conclusions:

• Accurate characterization of clonogenic nucleus sizes, particularly the smallest ones, is vital for reliable Alpha DaRT dosimetry.
• Small nucleus contributions are critical; their omission can lead to substantial underestimation of tumor control probability.
• Integrating nucleus size variability into microdosimetric models enhances prediction accuracy for alpha-based therapies.