Fetus-Specific Hematopoietic Stem Cell Dosimetry Framework for Leukemia-Relevant Target Cells During Prenatal...

Area of Science:

• Radiation dosimetry
• Developmental biology
• Hematopoiesis

Background:

• Hematopoietic stem cells (HSCs) are key targets for radiation-induced leukemia.
• Red bone marrow (RBM) is typically used for HSC dosimetry postnatally.
• Fetal HSCs distribute across multiple organs (liver, bone marrow), questioning RBM-only dosimetry accuracy.

Purpose of the Study:

• To develop a fetus-specific HSC dosimetry framework.
• To account for age- and organ-specific HSC distributions during fetal development.
• To evaluate the accuracy of RBM-only dosimetry in fetuses.

Main Methods:

• Updated fetal HSC distributions based on developmental biology, focusing on liver and bone marrow.
• Utilized Monte Carlo simulations with ICRP pregnant-female reference computational phantoms (MRCPs) and Geant4.
• Calculated photon dose coefficients for external exposure and specific absorbed fractions for internal exposure.

Main Results:

• At 8 weeks, HSCs were liver-localized, yielding zero RBM dose but substantial HSC dose.
• Significant discrepancies (up to 7.2-fold) between HSC and RBM doses occurred from 10-20 weeks due to fetal liver HSC dominance.
• Discrepancies diminished by 25-30 weeks as HSCs colonized bone marrow, becoming identical by 35-38 weeks.

Conclusions:

• Fetus-specific HSC dosimetry provides biologically informed dose estimates, highlighting RBM-only limitations in early/mid-fetal stages.
• The proposed framework supports prenatal radiation risk assessment for both external and internal exposures.
• Offers a more robust basis for evaluating fetal radiation-induced leukemia risk.