Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice.
The bone-seeking property and the potential exposure of red marrow by the alpha-particle emitter (223)Ra (half-life, 11.43 d) were compared with those of the beta-emitter (89)Sr (half-life, 50.53 d).


METHODS
The biodistributions of (223)Ra and (89)Sr 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 (89)Sr and (223)Ra selectively concentrated on bone surfaces relative to soft tissues. The measured bone uptake of (223)Ra was slightly higher than that of (89)Sr. At 24 h, the femur uptake of (223)Ra 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 (223)Ra than for (89)Sr. Although predominant clearance of (223)Ra was observed from the soft tissues within the first 24 h, the bone uptake of (223)Ra, which was not significantly different from maximum after only 1 h, was not significantly reduced during the 14 d. Furthermore, little redistribution of (223)Ra 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 (223)Ra alpha-emitter might have a marrow-sparing advantage compared with beta-emitters for targeting osteoid surfaces because the short-range alpha-particles irradiate a significantly lower fraction of the marrow volumes. At the same time, the bone surfaces will receive a therapeutically effective radiation dose.


CONCLUSIONS
The results of this study indicate that (223)Ra is a promising candidate for high-linear-energy transfer alpha-particle irradiation of cancer cells on bone surfaces. (223)Ra 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 beta-emitters.
Henriksen
Gjermund
G
Department of Chemistry, University of Oslo, Oslo, Norway.
Fisher
Darrell R
DR
Roeske
John C
JC
Bruland
Øyvind S
ØS
Larsen
Roy H
RH
D000512:Alpha Particles; D000818:Animals; D001610:Beta Particles; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000000981:diagnostic imaging; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D011883:Radium / Q000097:blood / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D012886:Skull / Q000000981:diagnostic imaging / Q000378:metabolism*; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism; D013324:Strontium / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; C025700:strontium chloride; D011883:Radium; D013324:Strontium