FEB 11, 2019 7:18 AM PST

Actinium-based Targeted Alpha Therapy Delivers A Combo Punch

WRITTEN BY: Daniel Duan

An actinium-225/ bismuth-213 generator operated by ORNL researchers Rose Boll  and Joseph Rayburn (Jason Richards/ORNL)

Radiotherapy is a staple among many medical interventions to treat cancer. Besides external beam radiotherapy and sealed radio-source therapy, it is common for oncologists to prescribe systemic administration of radioisotopes, through either injection or ingestion, for patients diagnosed with a variety of malignant tumors.

To launch a precisely located, energy-intensive assault against tumor tissues, targeted radiotherapy (TRT) is considered as a more favorable option as compared to the traditional non-targeting radioisotope treatment.

Combining a tumor-seeking vector (e.g. monoclonal antibodies or antibody fragments) and isotopes that release high energy particles, researchers have come up with a handful of clinically approved radiopharmaceuticals since the early 2000s, such as yttrium-90 labeled ibritumomab tiuxetan (Zevalin) and iodine-131 labeled tositumomab (Bexxar).

Although alpha (comprising of 2 protons and 2 neutrons) and beta (single electron) particle emitting isotopes are considered favorable, the former is more advantageous due to the fact that they travel much shorter distances in biological tissues, meaning only damaging cell in close proximity. What's more, with higher linear energy transfer, or (LET), the alpha-emitting isotopes can pack a more forceful punch than their beta-emitting counterpart.

Scientists have increasingly recognized the potential of two alpha emitters actinium-225 (Ac-225) and its “daughter” bismuth-213 (Bi-213) in TRT. When the "parent" isotope is delivered to the cancerous tissue, it decays and launches the first wave of attack; once the decay is finished, actinium turns into its "daughter" bismuth, which can launch a second attack to the targeted cells. 

The Department of Energy's Oak Ridge National Lab (ORNL) in Oak Ridge, Tennesee is among the only two locations in the world that are capable of producing Ac-225 for use in cancer therapy.  Ac-225 is a decayed product of another radioisotope thorium-229 (Th-229). In theory, to obtain pure Ac-225 one simply needs to remove the decayed isotope from its "parent". In reality, the radiochemical process is anything but straightforward. 

In the early 1990s, Radiochemist Saed Mirzadeh and colleagues first got their hands on a small amount of Th-229 as waste material from a 1960s reactor project. From there, they developed a complex purification method to extract pure Ac-225 from the Th-229, a process they called "milking the thorium cow".

Due to the increasing demand for Ac-225 as its TRT applications expanded, the current production process is not able to keep up. In 2012 a project was initiated to identify a different production method, with potentially a higher yield. Collaborating the Los Alamos and Brookhaven National Laboratories, a group of DOE scientists have successfully developed an alternative process. 

The new production involves bombarding natural thorium targets with high-energy protons using particles accelerators outside of ORNL. The bombarded targets were then shipped back to ORNL for extensive chemical processing. Since the start materials are no longer limited to reactor fuel wastes, the new method is capable of producing sufficiently pure actinium in a much larger quantity. Clinical trials using the Ac-225 produced in the new method are expected to commence sometime between 2018 and 2019.

Milking the Thorium Cow (Periodic Videos)

Source: Oak Ridge National Laboratory

About the Author
  • Graduated with a bachelor degree in Pharmaceutical Science and a master degree in neuropharmacology, Daniel is a radiopharmaceutical and radiobiology expert based in Ottawa, Canada. With years of experience in biomedical R&D, Daniel is very into writing. He is constantly fascinated by what's happening in the world of science. He hopes to capture the public's interest and promote scientific literacy with his trending news articles. The recurring topics in his Chemistry & Physics trending news section include alternative energy, material science, theoretical physics, medical imaging, and green chemistry.
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