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

Abstract

The biological effects of radionuclides that emit α particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of α-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy α particles (3.2 MeV) emitted by 148 Gd is investigated and determined to be 7.4 ± 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po and 212 Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for α particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE α = 9.14 − 0.510 E α , where 3 < E α < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific α-particle emitter 223 Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 ± 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E α relationship to predict the biological effects of α-particle emitters in Vivo.

Biological Response to Nonuniform Distributions of210Po in Multicellular Clusters

“…Therefore, similar findings should be anticipated for α-particle emitters with somewhat shorter physical half-lives. However, other aspects related to the dependence of RBE on emitted α-particle energies and chord-length distributions would have some impact on the survival curves (41,42).…”

203Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

“…The biodistribution of 203 Pb-DOTA-Re(Arg 11 )CCMSH over time was determined to evaluate uptake and retention and to calculate absorbed radiation doses from 203 Pb-DOTA-Re(Arg 11 )CCMSH in tumors, healthy organs, and tissues using methods described previously (15)(16)(17). Time-activity curves were generated for 16 organs and tissues (blood, bone, brain, heart, lung, liver, skin, spleen, stomach, kidney, large intestine, small intestine, muscle, pancreas, carcass, and tumor).…”

Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha-Particle Emitter Therapy

“…Because RBE depends on LET and LET depends on the α-particle energy, the RBE differs for particles emitted by different radionuclides (45). A number of possibilities can account for this dependence, for example: (1) RBE2(α/β) is determined experimentally as a function of initial α-particle energy over the range of energies emitted by the various α emitters (~2-10 MeV) (45) or (2) a more theoretical microdosimetric approach where RBE2(α/β) takes into account the changes in LET as the α-particles traverse the cell population.…”