First In Vivo Evaluation of Liposome-encapsulated ²²³Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

Abstract

Background: Liposomes carrying chemotherapeutics have had some success in cancer treatment and may also be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution and to estimate the radiation doses of the alpha emitter ²²³Ra loaded into pegylated liposomes in selected tissues. Materials and Methods: ²²³Ra was encapsulated in pegylated liposomal doxorubicin (PLD) by ionophore-mediated loading. The biodistribution of liposomal ²²³Ra was compared to free cationic ²²³Ra in Balb/C mice. Results: Liposomal ²²³Ra circulated in the blood with an initial half-life in excess of 24 hours, which agreed well with that reported for PLD in rodents, while the blood half-life of cationic ²²³Ra was considerably less than an hour. When liposomal ²²³Ra was catabolized, the released ²²³Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free ²²³Ra. Pre-treatment with non-radioactive PLD 4 days in advance lessened the liver uptake of liposomal ²²³Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Conclusion: Liposomal ²²³Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.