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Targeting of Osseous Sites with -Emitting ²²³Ra: Comparison with the ß-Emitter ⁸⁹Sr in Mice

¹ Department of Chemistry, University of Oslo, Oslo, Norway
² Anticancer Therapeutic Inventions AS, Oslo, Norway
³ Pacific Northwest National Laboratory, Richland, Washington
⁴ Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
⁵ Department of Oncology, Norwegian Radium Hospital, Oslo, Norway

The bone-seeking property and the potential exposure of red marrow by the -particle emitter ²²³Ra (half-life, 11.43 d) were compared with those of the ß-emitter ⁸⁹Sr (half-life, 50.53 d). Methods: The biodistributions of ²²³Ra and ⁸⁹Sr were studied in mice. Tissue uptake was determined at 1 h, 6 h, 1 d, 3 d, and 14 d after intravenous administration. Radiation absorbed doses were calculated for soft tissues and for bone. Multicellular-level doses were estimated for bone marrow cavities. Results: Both ⁸⁹Sr and ²²³Ra selectively concentrated on bone surfaces relative to soft tissues. The measured bone uptake of ²²³Ra was slightly higher than that of ⁸⁹Sr. At 24 h, the femur uptake of ²²³Ra was 40.1% ± 7.7% of the administered activity per gram of tissue. The uptake in spleen and most other soft tissues was higher for ²²³Ra than for ⁸⁹Sr. Although predominant clearance of ²²³Ra was observed from the soft tissues within the first 24 h, the bone uptake of ²²³Ra, which was not significantly different from maximum after only 1 h, was not significantly reduced during the 14 d. Furthermore, little redistribution of ²²³Ra daughter products away from bone was found (2% at 6 h and less than 1% at 3 d). Estimates of dose to marrow cavities showed that the ²²³Ra -emitter might have a marrow-sparing advantage compared with ß-emitters for targeting osteoid surfaces because the short-range -particles irradiate a significantly lower fraction of the marrow volumes. At the same time, the bone surfaces will receive a therapeutically effective radiation dose. Conclusion: The results of this study indicate that ²²³Ra is a promising candidate for high-linear-energy transfer -particle irradiation of cancer cells on bone surfaces. ²²³Ra can, together with its daughter radionuclides, deliver an intense and highly localized radiation dose to the bone surfaces with substantially less irradiation of healthy bone marrow compared with standard bone-seeking ß-emitters.

Key Words: -particle emitter • ²²³Ra • ⁸⁹Sr • bone targeting • dosimetry

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