Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The ^{224}{\rm Ra}$ daughters ^{212}{\rm Pb}$ and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable ^{208}{\rm Pb}$, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of ^{212}{\rm Pb}$ and its daughters. When ^{212}{\rm Pb}$, in equilibrium with its daughters 212 Bi, 212 Po and ^{208}{\rm Tl}$, was administered directly into the testis, the dose required to achieve 37% survival ($D_{37}$) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the $D_{37}$ for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: ${\rm RBE}_{\alpha}=4.8-6.1\times 10^{-2}\ {\rm LET}+1.0\times 10^{-3}\ {\rm LET}^{2}$. Similarly, the dependence of RBE on α-particle energy $E_{\alpha}$ was given by ${\rm RBE}_{\alpha}=22\ E_{\alpha}^{-0.73}$. These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters.