Biological Effect of Lead-212 Localized in the Nucleus of Mammalian Cells: Role of Recoil Energy in the Radiotoxicity of Internal Alpha-Particle Emitters

Abstract

The radiochemical dipyrrolidinedithiocarbamato-212 Pb(II) [ 212 Pb(PDC) 2 ] is synthesized and its effects on colony formation in cultured Chinese hamster V79 cells are investigated. The cellular uptake, biological retention, subcellular distribution and cytotoxicity of the radiocompound are determined. The 212 Pb is taken up quickly by the cells, reaching saturation levels in 1.25 h. When the cells are washed, the intracellular activity is retained with a biological half-life of 11.6 h. Gamma-ray spectroscopy indicates that the 212 Pb daughters ( 212 Bi, 212 Po and 208 Tl) are in secular equilibrium within the cell. About 72% of the cellular activity localizes in the cell nucleus, of which 35% is bound specifically to nuclear DNA. The mean cellular uptake required to achieve 37% survival is 0.35 mBq of 212 Pb per cell, which delivers a dose of 1.0 Gy to the cell nucleus when the recoil energy of 212 Bi and 212 Po decays is ignored and 1.7 Gy when recoil is included. The corresponding RBE values compared to acute external 137 Cs γ rays at 37% survival are 4.0 and 2.3, respectively. The chemical Pb(PDC) 2 is not chemotoxic at the concentrations used in this study. Because the β-particle emitter 212 Pb decays to the α-particle-emitting daughters 212 Bi and 212 Po, these studies provide information on the biological effects of α-particle decays that occur in the cell nucleus. Our earlier studies with cells of the same cell line using 210 Po (emits 5.3 MeV α particle) localized predominantly in the cytoplasm resulted in an RBE of 6. These earlier results for 210 Po, along with the present results for 212 Pb, suggest that the recoil energy associated with the 212 Bi and 212 Po daughter nuclei plays little or no role in imparting biological damage to critical targets in the cell nucleus.

MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations

“…However, the 0.1% cutoff was implemented neither for the spectrum of b particles nor for Auger electrons. The recoil energy of the residual daughter after a decay was not included because experiments indicate that this energy is not biologically relevant (36). The "b Average Energy Spectrum" option provides the radiation data contained on the compact disk that accompanies the second edition of MIRD: Radionuclide Data and Decay Schemes (37).…”

Monte Carlo simulation of irradiation and killing in three-dimensional cell populations with lognormal cellular uptake of radioactivity

“…These were both assigned a value of 0.64 Gy which corresponds to the experimental dose required to achieve 37% survival ( D 37 ) when 100% of the cells were labeled with 210 Po-citrate, an emitter of 5.3 MeV alpha-particles (Neti and Howell 2007). The assumption of D 37,self = D 37,cross derives from our previous studies which showed equivalent RBE values for intranuclearly and cytoplasmically localized alpha emitters (Azure et al 1994). A Monte Carlo method was used to determine whether a given target cell suffered radiation-induced cell death (Rajon et al 2011).…”

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

“…Although there is considerable experimental data on the biological effects of α particles in vitro (35)(36)(37)(38)(39)(40)(41)(42), there is a dearth of in vivo data that systematically explore the dependence of RBE on the energy of α particles emitted by incorporated radionuclides. In this work, an empirical RBE-E α relationship was obtained using spermatogenesis in mouse testes as the experimental model and survival as the biological end point.…”