Radium-223

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Radium-223 ( Ra-223 , ²²³ Ra ) is a radium isotope with a half-life of 11.4 days -life , in contrast to the more common radium-226 isotope found by Curies, which has a half-life of 1601 years. The main use of radium-223, as radiofarmaka to treat metastatic cancer in bone, takes advantage of its chemical similarity with calcium, and the short distance of the emitted radiation of alpha.

Video Radium-223

Origin and preparation

Although radium-223 is naturally formed in trace amounts by uranium-235 decay, it is generally made artificially, by exposing the 226-natural radium to neutrons to produce radium-227, which decays with 42 minutes part-time for acts. -227. Actinium-227 (half 21.8 years) in turn decays through thorium-227 (half-life of 18.7 days) to radium-223. This decay line makes it convenient to prepare radium-223 by "flushing" from a generator containing acryl-227 or "cow", similar to the widely used moly cow to prepare technically important medallion-isoton isotope.

Maps Radium-223

Medical use

Pharmaceutical products and medical use of radium-223 against bone metastasis were discovered by Roy H. Larsen, Gjermund Henriksen and ÃÆ'ËÅ"yvind S. Bruland and have been developed by the former Norwegian company Algeta ASA, in partnership with Bayer, under the trade name Xofigo (formerly Alpharadin ), and is distributed as a solution containing radium-223 chloride (1100 kBq/ml), sodium chloride, and other ingredients for intravenous injection. Algeta ASA was later acquired by Bayer who is now the sole owner of Xofigo. The recommended regimen was six treatments of 55 kBq/kg (1.3 uCi per kg), repeated at 4-week intervals.

Action mechanism

The use of radium-223 to treat metastatic bone cancer depends on the ability of alpha radiation from radium-223 and short-lived decay products to kill cancer cells. Radium is typically absorbed by bone based on its chemical similarity with calcium, with most of the radium-223 not taken by the cleansed bone, especially through the intestine, and excreted. Although radium-223 and its decay products also emit beta and gamma radiation, more than 95% of the decay energy is in the form of alpha radiation. Alpha radiation has a very short range of tissue, about 2-10 cells, compared to beta or gamma radiation. This reduces damage to surrounding healthy tissue, producing a more localized effect than the beta-emitter strontium-89, also used to treat bone cancer. Considering preferential absorption by bone and short distances of alpha particles, radium-223 is thought to provide osteogenic cells that target radiation doses at least 8 times higher than other non-targeted tissues.

Clinical trials and FDA approval

Phase II studies of radium-223 in patients with cervical-resistant prostate cancer (CRPC) with bone metastases showed minimal myelotoxicity and good tolerance for treatment.

²²³ Ra succeeded in reaching the ultimate end point of overall survival in patients with phase III ALSYMPCA (ALpharadin in Symptom Prostate SYMptomatic patients) for bone metastases produced from CRPC in 922 patients.

The ALSYMPCA study was discontinued early after a preliminary analysis of its planned efficacy, following recommendations from the Independent Data Monitoring Committee, on the basis of achieving statistically significant increases in overall survival (two sides p-value = 0.0022, HR = 0.699, survival average overall life was 14.0 months for ²²³ Ra and 11.2 months for placebo). The initial phase II of the trial showed a 4.5 month increase in survival. A figure lower than 2.8 months improving survival in phase III, is likely the result of stopping the trial. Survival time for surviving patients can not be calculated.

In May 2013, ²²³ Ra received marketing approval by the US Food and Drug Administration (FDA) as a treatment for CRPC with bone metastasis in patients with symptomatic bone metastases and without known visceral disease. ²²³ Ra received priority review as a treatment for unmet medical needs, based on its ability to extend overall survival as demonstrated in Phase III trials.

The study also led to approval in the European Union on September 19, 2013

²²³ Ra also showed promising early results in phase IIa trials with bone metastases from breast cancer that no longer respond to endocrine therapy. Data show that ²²³ Ra reduces bone alkaline phosphatase (bALP) levels and urine N-telopeptide (uNTX), a key marker of bone reshuffling associated with bone metastasis in breast cancer.

Side effects

The most common side effects reported during clinical trials in men who received ²²³ Ra were nausea, diarrhea, vomiting and swelling of the feet, ankles or feet. The most common disorders detected during blood tests are anemia, lymphocytopenia, leukopenia, thrombocytopenia and neutropenia.

Other radium-223-based compounds

Although radium does not readily form a stable molecular complex, there have presented data on methods to improve and adjust the specificity for certain cancers by connecting to monoclonal antibodies, by attaching ²²³ Ra in liposome cushioning antibodies on their surface.

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See also

• Radium chloride

src: clincancerres.aacrjournals.org

References

src: www.degruyter.com

External links

• Information of the US National Institute of Health an Alpharadin
• Algeta Information about Xofigo
• Participation of phase III studies of Alpharadin
• Alpharadin information from researcher Professor Oyvind S. Bruland
• "FDA approves new drugs for advanced prostate cancer". US FDA. Archived from original on 2013/05/15

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