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Radium-223: A Molecular Smart Bomb for Prostate Cancer Bone Mets

Prostate cancer bone metastasis

Roughly 11-12% of men will be diagnosed with prostate cancer (PCa) in their lifetime. Upwards of 20% of treated patients will eventually experience recurrence. One out of 41 PCa patients will die from the disease, since PCa has the ability to metastasize (spread) to distant organs and skeletal sites. In fact, bone is a “preferred” location for metastasis. When the cancer establishes a tumor in the bone, it is called prostate cancer bone metastasis, or PCa bone mets. This distinguishes it from primary bone cancer (cancer that begins in the bone), which is quite rare.

Hormone resistant PCa bone mets

Until fairly recently, there were few effective methods to target and treat bone mets. The existing treatments were systemic, that is, dispersed throughout the body in hopes of retarding the progression and spread of PCa, including bone mets. The two prevailing systemic treatments have been:

  1. Androgen deprivation therapy (ADT, also called hormone therapy or chemical castration) – This approach used pharmaceuticals to cut off the supply of testosterone (a male hormone, or androgen) so the cancer was deprived of fuel. This is not a cure, but it is effective in halting further PCa activity for some period of time. Eventually, the cancer cells develop resistance to the treatment and renew their growth. This is called hormone-refractory PCa because it no longer responds to ADT.
  2. Chemotherapy – This approach uses medications that are toxic to cancer cells, but since they can also harm healthy cells, there can be side effects.
    The challenge has been how to treat PCa bone mets once ADT is no longer effective in a more precise fashion than a systemic therapy.

Molecular radiotherapy

New hope for treating PCa bone mets exists in the form of “smart molecules” that are “loaded” with a radioactive substance that is lethal to PCa. It’s called molecular radiotherapy. It’s like a “smart bomb” that has a guidance system so it can deliver an explosive payload to a very precise target. The FDA has now approved such a therapy specifically for advanced hormone-refractory PCa bone mets. It is called Xofigo®. It can be used alone or in combination with other protocols, and has been shown to dramatically increase survival over hormone therapy alone.

Here’s the principle behind it: When PCa cells colonize bone, they greedily hijack minerals, such as calcium, and other growth factors used by healthy bones to build new bone cells as old ones are disposed of. These busy tumor cells become an area of unusually concentrated mineralization. Therefore, if a man-made substance that mimics calcium but is armed with an anti-cancer weapon, the hyper-concentrated activity would attract the molecule to the greedy cancer cells that would absorb it. The weapon would then accomplish its task, and the cells would die off.

In this case, the weapon is a radioactive isotope called radium-223 (223Ra). When injected by IV, it

…acts as a calcium analog and about 25% is taken up by bone. It concentrates in sites of active mineralization with high osteoblastic activity… 223Ra is mainly excreted by the gastrointestinal tract, and <1% of the injected activity remains in the blood 24 hours after injection.1

Put simply, 223Ra mimics calcium. The industrious bone-building and bone-destroying PCa tumor cells take it up. The very short-range, short-lived radioactivity damages each cancer cell’s DNA before the radioactivity fades away, and within 24 hours over 99% of it is gone, leaving the cells unable to reproduce and to slowly die off. The tumor shrinks, pain is often relieved, and survival is prolonged. Since it is a targeted treatment, it reduces the burden of disease in the bone. However, it does not cure all the hormone-refractory PCa elsewhere in the body.

MRI-guided Focused Ultrasound (MRgFUS) to treat bone mets

There is a another type of targeting destructive force to PCa bone mets. It destroys individual metastatic bone tumors and relieves the pain they cause using lethal heat. It is called MRI-guided Focused Ultrasound (MRgFUS). This outpatient treatment involves no surgery or radiation. Instead, under MRI guidance, beams of ultrasound are aimed at the bone tumor from numerous directions. They pass harmlessly through skin and other tissue, but when they precisely meet at the tumor, they create sufficient heat to destroy the tumor and its nerves that send pain signals to the brain.

The Sperling Medical Group offers MRgFUS for the treatment of metastatic bone disease. Visit our website for more information.

1 Deshayes E, Roumiguie M, Thibault C, Beuzeboc P et al. Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017; 11: 2643–2651.

Bone mets