Radioactivity against cancer? This very promising new European track – L’Express

For his first actinium 225 injection, he arrived in a wheelchair. For the second, he came on crutches. During the third, he walked alone. And after the fourth and final, he returned home, climbed a tree in his orchard and picked oranges. All without having suffered from the violent nausea and fatigue that had shaken him during his chemotherapy. This Spanish patient suffered from an advanced form of prostate cancer against which all other treatments had failed. His spectacular recovery and his testimony had a profound impact on the researchers behind the discovery of treatment with actinium 225, a radioactive isotope known as an “alpha emitter” which, once administered into the human body, clings to cells. cancerous and emits radioactive radiation which irradiates and kills them.

Radioactivity against cancer? The idea seems counterintuitive, as nuclear power is traditionally associated with energy production and the risks of causing… cancer! However, for more than fifteen years, research in this area has also been used to improve care and health, in particular thanks to various technologies making it possible to detect this disease, including scanners. In recent years, new avenues have been developed to use radioactivity to eliminate tumors. Alongside external radiotherapy, which uses beams of radiation to target cancer cells, there are now internal radiotherapy techniques.

Pharmaceutical giant Novartis was the first to enter this new field of medicine, with two drugs that treat prostate cancer and neuroendocrine tumors (a rare cancer that forms networks of tumors that can arise anywhere in the body). ) thanks to lutetium 177, a radioactive atom called a “beta emitter”. It targets and irradiates cancer cells, including metastases, but much more precisely than external beam radiotherapy. However, if this treatment sometimes proves effective, it is not without fault. It does not work for all types of cancer or for all patients and, while it often adds a few extra years of life, does not always eliminate all metastases.

Actinium 225, “1,000 times more effective” than lutetium 177

Researchers from the Joint Research Center (JRC), the European Union’s scientific and technical research laboratory, therefore decided to perfect the idea. In recent years, they have succeeded in developing a new treatment using the famous actinium 225. “The first tests indicate that it is a thousand times more effective than lutetium 177”, assures Rachel Eloirdi, director of the JRC unit responsible for this technology.

The principle of actinium 225 therapy remains the same: it involves injecting a drug into patients’ bodies that will irradiate cancer cells. “They have very specific receptors on their surface. We developed vectors (in particular antibodies) which recognize these receptors and attach to them naturally, a bit like magnets. Then we attached our alpha isotope, actinium 225 , together, the vector and the isotope can identify cancer cells and kill them using radioactive radiation. continues Rachel Eloirdi.

The interest of the alpha emitter is that it emits phenomenal doses of energy, much more than lutetium 177, but over a shorter distance: no more than a few cells, or a few tens of micrometers. In other words, actinium 225 is more powerful, more precise, and poses little risk of harming healthy cells. Additionally, it causes almost no side effects, unlike other cancer treatments like chemotherapy.

But is it completely risk-free? “To be precise, it is not possible to control when the radioactive atom fires in the body, so once the product has been injected, a few atoms may activate before reaching their target. But this does not represent any risk: it is when they gather in numbers around a cancer cell that their combined radiation is powerful enough to kill it,” explains Sven Van den Berghe, former physicist at the Belgian Nuclear Research Center who collaborates with the JRC, and is now CEO of PanTera, a start-up that produces actinium 225.

Around ten clinical trials with promising results

The JRC has launched around ten clinical trials aimed at testing actinium 225 on patients thanks to partnerships established with European hospitals – notably in Marseille and Nantes -, to whom they provide their technology, treatment and training. doctors. For the moment, these trials are still in the preliminary phase (phase I or phase II). Given European rules, this treatment can therefore only be administered as a last resort, once all other solutions have failed. At this stage, patients are often affected by advanced or even generalized cancers.

But researchers are hopeful of moving quickly into phase III, which will allow this treatment to be more widely used. Because actinium 225, originally developed to treat patients with prostate cancer – the second most common male cancer in the world – gives very promising results. To date, more than 1,000 patients have been treated in compassionate use programs, most often with success, including complete remissions. JRC researchers have also published a notable study in The Lancet Oncology in January 2024 which details these results. However, this technology remains little known today.

“During a recent conference given at the Rencontres de l’esprit critique (REC), in Toulouse, I asked those who had already heard of radiotheranostics or alpha targeted therapy to raise their hands. To my great delight Surprise, there was almost no one there, deplores Rachel Eloirdi. It is important to provide information on the subject and spread the message of hope about this new treatment against cancer, even if there is still a lot to do. .”

A collaboration carried out with the Medical University of Warsaw, in Poland, is also exploring the potential of actinium 225 on brain cancer with, here again, promising results on more than 100 patients treated. And the JRC does not intend to stop there, since it also hopes to be able to adapt the treatment to breast cancer.

Researchers also hope that future therapies combining beta and alpha emitters may prove even more effective. “For me, these combinations are the future, but it is more complex to carry out clinical trials with this combination, so we will have to be patient,” says Sven Van den Berghe.

The production and the price in question

Scientists nevertheless warn of two difficulties. The first is linked to the production of the necessary quantity of actinium 225 in order to treat patients on a large scale. Indeed, a growing number of clinical research centers around the world recognize the potential of targeted alpha therapy. Demand for these radioactive compounds is therefore expected to increase significantly in the coming years. Answering them will be essential to making medical radionuclide technologies accessible to all. “We need to produce a lot more actinium 225,” confirms Rachel Eloirdi.

“Today, we produce a quantity of actinium throughout the world equivalent to 2,500 or 3,000 patients per year maximum, it is too little,” warns Sven Van den Berghe, convinced that actinium 225 represents the future of cancer therapy. Reason why he became the CEO of the start-up PanTera which specializes in the production of this radioisotope. His company plans its first deliveries to hospitals conducting clinical trials this year. Large quantity production, thanks to its factory located in Mol, near the Belgian Nuclear Research Center, is planned for 2028.

The second difficulty is linked to price. If the JRC produces actinium 225 without profit, it will not be the same for pharmaceutical producers who will seize the technology. However, the latter traditionally consider that the cost of raw materials used to manufacture a drug should not exceed 1 to 2% of the final price. “But for actinium, this percentage must be around 10%, otherwise it will not be possible to ensure production, which is expensive and restrictive,” argues Sven Van den Berghe. The future of actinium 225 will therefore require lobbying by scientists and doctors, to convince pharmaceutical groups to cut their margins.