The radioisotope actinium-225 is said to be the “rarest drug on Earth.” Connect it to a cancer-targeting molecule, and it has shown incredible potential as a precise treatment for terminal late-stage prostate cancer. But there’s only enough of it to treat around 1,700 patients a year, if we could harvest the entire world’s supply.
That’s because only miniscule amounts of it occur in nature, and until now we’ve been collecting it as a decay product from thorium-229 — another radioisotope found in aging nuclear weapons and spent nuclear fuel. This method only produces the weight equivalent of a few grains of sand each year, and ramping up production of nuclear waste just to make more of the drug isn’t exactly the cleanest option.
There is, however, another pathway to get to actinium-225, and cyclotron particle accelerator at TRIUMF had been making with unknowingly in the course of its everyday experiments.
Actinium-225 has a half life of just 10 days, and as it decays it shoots out an alpha particle with enough force that it can tear through the DNA of a nearby cancer cell.
Although there are other radioisotopes that release alpha particles, actinium-225 fits the perfect profile for adaptation to cancer therapy: after it decays, its byproduct is non-toxic, it can easily be chemically attached to a targeting molecule, and it is stable for just the right amount of time to get to a cancer cell before decaying.
TRIUMF in Vancouver is home to the world’s largest cyclotron particle accelerator. At 18 m in diameter, it can send charged particles like protons through a spiral 45 km long, accelerating through magnetic fields as they go. Protons can reach speeds of up to 75 percent of the speed of light. When they collide with other particles, they can create rare materials, some of which are only stable for fractions of a second.
At the end of the track is the beam dump: an aluminum block that safely absorbs the high-speed proton beam left over after an experiment. Actinium-225 was one of the many by-products left in the beam dump.
This is one of the only places in the world where actinium-225 can be made using this process, and we can intentionally make more of it by irradiating a thorium-232 disc with trillions of high-speed protons. On impact, the thorium can split into any possible element lighter than itself, including actinium.
The disc is later dissolved in acid to make a soup of all the products, and the actinium-225 is purified from there for use as a drug.
Conservatively, the researchers at TRIUMF estimate that they will be able to produce 100 times the current annual global supply.
In partnership with Fusion Pharmaceuticals, a start-up company founded at McMaster University, the project also has the connections to build targeted platforms to deliver the actinium precisely to the desired cancer sites. Fusion is a Canadian leader in targeted alpha therapies.
Until now, the uses of actinium-225 therapies have been limited to experimental compassionate use, when terminal patients have otherwise been at the end of their lives. With increased supply, larger clinical trials will become possible, with possible expansion from prostate cancer to other cancer types.
“Through this collaboration agreement, we are partnering with a premier developer of innovative radiotherapies to deepen TRIUMF’s leadership position in isotope production,” said TRIUMF Innovations Chief Executive Officer Kathryn Hayashi in a press release.
“The results that stem from this partnership may dramatically advance the treatment of cancer as we know it, and it is exciting to imagine how this work could change the lives of countless Canadians and others around the world.”