Figure 1 Posterior view of a whole-body bone scan of a 54-year-old male patient with ankylosing spondylitis, acquired three hours after injection of 600 MBq of 99mTc-HDP (99m technetium-hydroxy-methylene-phosphonate). Multifocal areas of enhanced bone metabolism are prominent in the entire spine, which is consistent with clinical symptoms of pain and impaired mobility.

intensity of calcium metabolism, which is elevated in areas of pathological ossification during AS. In an adult, approximately 25% of the injected dose is incorporated in the skeleton, 55% in a 10-year-old child and 75% in an infant (19). The radionuclide is mainly deposited on the surface area of the bone, that is, under the endosteum, the periosteum, and in the zones of compact bone undergoing bone remodeling.

224Ra is both an a- and a y-emitter. It decays with a physical half-life of 3.64 days into further daughter nuclides, which send out not only a particles, but also ยก3 particles and y radiation to some extent. The final product of this radioactive decay is 208Pb, which is stable, inert, and unobjectionable in the given dose from both a toxicological and a pharmacological point of view. Owing to its high osteotrope affinity, 224Ra is enriched in sites of active bone formation in the skeleton, and blocks the secretion of proinflammatory cytokines in the course of activated autoimmune processes. Depending on the short range of the a particles in the tissue of approximately 50 mm, for example, only a few cell diameters, the radiation dose to other tissues, especially to the bone marrow, is acceptably low. A direct inhibition of pain-mediating nerve fibers is not an assumed mechanism of action, as the nervous system is generally thought to be relatively resistant to radiation. By blocking the inflammatory cytokines, ongoing mineralization processes are inhibited in addition to the anti-inflammatory and analgetic results. Antiosteoblastic effects were frequently discussed for 224RaCl, but have not been proven to date. Whole-body skeletal uptake of 99mTc-HDP is unchanged after treatment of AS with 224RaCl compared with the uptake values prior to therapy, suggesting no significant changes in bone metabolism in general (20).

Uptake of 224Ra into the bone is very fast with only 8% of the injected dose remaining in the circulating blood after 15 minutes. Eight hours after injection, only 1.5% is still found in the blood. This unbound 224RaCl is excreted up to 95% via the feces, and up to 5% via the urine.

The industrial production of 224RaCl from highly pure 228Th today is safe and reproducible. Highly developed quality controls assure the absence of significant contaminations with long-lasting radionuclides. 224RaCl must not be mixed with other drugs. In particular, any comedication with calcium or phosphate should be discontinued because of the decreasing bone uptake of 224Ra due to competitive binding effects.

0 0

Post a comment