Killing cancer cells with alpha particles could be the next step in treatment

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Canadian cancer researchers are part of the global effort to test targeted alpha therapy, a new form of treatment that some oncologists say will be the next step in attacking cancer at the cellular level.

Targeted alpha therapy shreds the DNA of cancer cells using radioactive alpha particles, which researchers say is more powerful at killing cancerous tumors than comparable existing treatments and less damaging to healthy tissue.

While no targeted alpha therapies have yet been approved for use outside of a clinical trial, several are in the final stages of testing and could be ready for consideration by Health Canada and international regulators within a few years.

Researchers see its potential in treating pancreatic, prostate and breast cancer, as well as the rarer neuroendocrine cancer, which affects the cells that regulate hormone production throughout the body.

Targeted alpha therapy “is another line of treatment that offers more hope for cancer patients,” says Dr. François Bénard, professor in the department of radiology at the University of British Columbia in Vancouver and a leading scientist at the BC Cancer Research Institute.

“It can prolong life, reduce symptoms and improve the well-being of people affected by cancer,” Bénard said in an interview.

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Promising new search-and-destroy cancer treatment tested in Canada

Researchers hope that targeted alpha therapy – now undergoing clinical trials in Canada – will become the future of cancer treatment. This therapy detects and kills cancer cells without damaging healthy cells.

Targeted alpha therapy falls within the same general category of the advanced cancer treatment known as cancer radioligand therapyin which specially designed molecules that bind only to cancer cells are injected into the body and release radioactive particles that kill the tumors.

The approved treatments in this category use isotopes that emit beta particles. What makes targeted alpha therapy a potential advancement is that alpha particles emit more powerful radiation over a shorter range.

'Like throwing a bowling ball'

Bénard compares existing radiopharmaceutical treatments that emit beta particles to throwing golf balls into a greenhouse: they can travel quite a distance and cause all kinds of damage along the way.

In contrast, says Bénard, targeted alpha therapy is “like throwing a bowling ball. So it will do a lot more damage, but in a much more limited area.”

Dr. Gerald Batist, director of the Segal Cancer Center at the Jewish General Hospital in Montreal, is participating in several clinical trials treating various cancers with targeted alpha therapy.

“The dimensions of their potential impact are only now being explored,” Batist said in an interview.

One of Batist's clinical trials is testing a method of treating prostate cancer by embedding beads loaded with alpha particles at the site of pancreatic cancer.

Although alpha particles carry powerful radiation, they cannot penetrate the skin and can even be blocked by something as thin as paper.

As a result, targeted alpha therapy does not have to take place in the type of protective bunker where traditional radiation therapy takes place.

“I'm really excited about it,” Batist said. “If we can treat people without having to take them to the hospital, or use these deep bunkers for any type of tumor, it will be a very big change for our healthcare system.”

3 Canadian locations in alpha therapy trial

Batist is also working on a targeted alpha therapy clinical trial which takes place at nearly 50 locations around the world, including the Sunnybrook Health Sciences Center in Toronto and the London Health Sciences Center in London, Ont. It investigates the use of the alpha-emitting radioactive isotope actinium-225 on neuroendocrine cancer.

In London, the research team led by nuclear oncologist Dr. David Laidley enrolled five patients in the trial, one of whom became the first person in Canada to be treated with actinium-225.

“Because these actinium particles are extremely powerful and emit a lot of radiation at a very short distance, we are really able to do a significant amount of damage to those tumors,” Laidley said in an interview.

“We have high expectations that the trial will be successful,” he said. “Once it's done, we obviously have to see it go to Health Canada for approval.”

Multiple companies in late-stage clinical trials

Bénard, who is not personally involved in clinical trials of targeted alpha therapy, describes it as an evolution in cancer treatment rather than a revolution because it builds on recent technological advances in creating the molecules that can transport radioactive isotopes into cancer cells .

“What we're seeing for the first time is multiple companies advancing these compounds through late-stage clinical trials to gain approval,” Bénard said. “It's very exciting because it's getting closer to the finish line.”

If and when treatments are approved, challenges remain in making targeted alpha therapy widely available.

Only a handful of sites worldwide are capable of producing the rare radioactive isotopes that emit alpha particles and can be used to treat cancer. One of these is TRIUMF, the particle accelerator in Vancouver, which is owned and operated by a consortium of Canadian universities.

Then there are the costs, expected to run into the tens of thousands of dollars per dose, putting provinces in the position of deciding whether to cover the treatment.

Consider the price of approved radiopharmaceutical treatments targeting neuroendocrine cancer (Lutathera) and prostate cancer (Pluvicto). Both kill cancer cells with the radioactive isotope lutetium-177, which emits beta particles.

Lutathera fees $35,000 per dosePluvicto costs $27,000 per dosewith a typical treatment course for each ranging from four to five doses.

Although The Canadian Medicines Agency has recommended that provinces cover both Lutathera And Pluvictonot all provinces do that, and negotiations between the drug manufacturer and the provinces are taking place this week. pan-Canadian pharmaceutical alliance above Pluvicto collapsed without agreement.

Pharma giants spend billions

A sign of how strongly the pharmaceutical industry believes in the future potential of targeted alpha therapy is the amount of money being spent in the sector lately.

“Drug companies are betting that delivering radiation directly to tumors will be the next big breakthrough in cancer,” says CNBC reported in September, pointing to some $10 billion in recent deals by major players such as Eli Lilly, AstraZeneca and Bristol Myers Squibb to buy or partner with companies developing radiopharmaceuticals.

Swiss drug manufacturer Novartis spent for about $6 billion, the US will buy the two radiopharmaceutical startups that Lutathera and Pluvicto developed.