Radiation dose to trabecular bone marrow stem cells from³H,¹⁴C and selected α-emitters incorporated in a bone remodeling compartment

Abstract

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for (3)H, (14)C and a set of alpha-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 microm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 microm endosteum for (3)H, (14)C and alpha-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal alpha-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

“…The age-dependent alpha-particle dosimetry of hematopoietic marrow, rather than red marrow, was first carried out employing analytical methods (Richardson et al 1991), whereas more sophisticated Monte Carlo simulations enable alpha-and beta-radiation dosimetric analyses of the skeleton, both in the quiescent (Eckerman and Stabin 2000, Richardson and Du-beau 2003, Watchman et al 2005) and remodelling states (Richardson et al 2007, Nie and Richardson 2009). For a minority of radionuclides and compounds, the dose to hematopoietic marrow and adipocytes can be markedly different and at variance with the average dose to homogeneous red marrow.…”

“…Increasing the peripheral marrow layer from 10 μm to 50 μm will affect the alpha particle dose to the bone cancer target from activity located in trabecular bone or marrow (Nie and Richardson 2009). This is due to the limited maximum range of alpha particles, e.g., 10 μm in soft tissue for 144 Nd, 1.8 MeV particles and 90 μm for 212 Po, 8.8 MeV.…”

“…The same is true for low energy, shorter-range beta-emitters, such as 14 C with a mean range of 40 μm in water. Alpha-particle activity was modeled by Nie and Richardson (2009) as a uniform source in bone marrow, bone volume and on bone surface. The ICRP's decision to move to a 50 μm marrow layer results in a relatively small increase in dose to the bone cancer target from alpha-emitters deposited in marrow, e.g., Thorotrast.…”

“…Firstly, new dosimetric methods are needed to assess the radiation dose to the peripheral marrow associated with both the quiescent bone surface and bone remodelling. Nie and Richardson (2009) conducted a dynamic simulation that studies the temporal changes of short-range radionuclides incorporated in a trabecular bone remodelling compartment. This compartment consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells.…”

“…This paper was written to meet the challenge set in 2007 by the ICRP Task Groups on Internal Dosimetry (INDOS) and Dose Calculation (DOCAL) to provide supporting biological and epidemiological evidence for proposed partitioned bone cancer and leukaemia targets. Nie and Richardson (2009) modeled the dose to stem/progenitor cells adjacent to the trabecular bone remodelling compartment and found this site to be a more likely candidate target for radiation-induced bone cancers, especially in childhood, than the ICRP target (i.e., the peripheral marrow adjacent to quiescent bone surfaces). This new target is based on the risk of bone cancer being higher when bone turnover is elevated: this is the case in the young rather than the old, in trabecular rather than cortical bone, and in association with hyper-metabolic pathology such as Paget's disease (osteitis deformans or osteodystrophia deformans).…”