Biodistribution of (225)Ra citrate in mice: retention of daughter radioisotopes in bone.

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Nucl Med Biol 2005 Nov; 32(8):859-67.


Alpha-particle-emitting radionuclides have potential for therapy of localized disease due to their high linear energy transformation and short pathlengths. Radiometals that home naturally to bone can be exploited for this purpose, and (223)Ra (t(1/2)=11.4 days) recently has been studied for therapy of bone tumors in mice and rats. Actinium-225 (t(1/2)=10 days) is also an attractive radioisotope for endoradiotherapy. In a single decay of a (225)Ac nucleus and its subsequent decay daughters, over 27 MeV ( approximately 90% of total energy) is released by sequential emission of four alpha particles, ranging in energy from 5.7 to 8.4 MeV. Although Ac(3+) does not home naturally to bone, its parent radioisotope (225)Ra (beta(-), t(1/2)=15 days) can be used as an in vivo source for (225)Ac. Thus, injection of (225)Ra takes advantage of the bone-homing properties of radium coupled with the significant amount of energy released from the (225)Ac decay chain. Our data confirm that a large fraction of radium citrate injected intravenously into mice localizes rapidly in bone. Injected doses per gram (ID/g) for (225)Ra range from 25% in skull to about 10% in sternum. Once deposited, the (225)Ra remains in the bone with a biological half life of >40 days. Furthermore, >95% of the daughter radioisotope, (225)Ac, is retained in the bone. However, a significant fraction of one of the daughter radioisotopes, (213)Bi, is found in kidney. The biodistribution data indicate that (225)Ra injection should be a powerful agent for killing cells associated with bone; however, the toxicity of this radioisotope which is similar to that of other alpha emitters limits the dose that can be tolerated.