This potential cancer treatment requires modern alchemy| Trending Viral hub

in a part of Los Alamos National Laboratory (LANL), which some call the Mesa, a beam of protons is shot down a mile-long tunnel through the New Mexico landscape. The particles move so fast that if they were not confined within the structure, they could circle the Earth 2.5 times in a second.

Five different facilities in the laboratory “sip” from this beam, extracting the protons they need for various experiments. One of them, called the Isotope Production Facility, smashes protons into a stationary target. The protons embed themselves in the target’s atoms and transmute them into new elements.

The Isotope Production Facility is currently involved in a positive (pun intended) effort for the medical industry: producing a substance called actinium 225an isotope with 89 protons and 136 neutrons. Isotopes They are different forms of the same element that have the same number of protons but different numbers of neutrons; The most common actinium isotope is 227, with two more neutrons than 225. Isotopes are radioactive. when their nuclei are unstable, with a nervous combination of protons and neutrons, and they are freed from excess energy by emitting alpha, beta or gamma rays. The particular radioactivity of actinium 225 is potentially powerful in the fight against prostate cancer, and studies are being conducted on its effectiveness against other malignancies. Although there are many radioactive isotopes, the emissions of actinium 225 are strong enough to damage cancer cells without causing as much damage to healthy ones. And this isotope dissipates in just the right amount of time, does its job, and then decays.

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For years, scientists have produced this species of actinium by waiting for thorium (element 90, with one more proton than actinium) to decay. But that method is slow and doesn’t produce much at once. If the U.S. Food and Drug Administration approves cancer treatments using actinium 225, currently in clinical trials, the old way of doing things likely won’t meet demand.

Anticipating the possible need for actinium production to jump to a new energy level, the Department of Energy created a program in 2015 to develop new production methods in larger batches, bringing together LANL, Oak Ridge National Laboratory (ORNL) in Tennessee and Brookhaven National Laboratory. in upstate New York in the effort. Since then, the laboratories have been constantly working on the project, hoping to be ready when the medical industry is.

As actinium 225 decays, it emits radiation in the form of alpha particles (two protons and two neutrons united). Kirk Rector, LANL program director and the laboratory’s point of contact for the Department of Energy’s Isotope Program, calls these particles “wrecking balls.” The energy they create is strong enough to break strands of DNA like a lightsaber cutting through two jump ropes in a game of double dutch.

But alpha particles are heavy (at least for particles), so they don’t travel very far (as far as a few membrane-coated cells), which means doctors can direct radiation therapy to the right place and limit damage to surrounding tissue. . Additionally, actinium 225 has a half-life of just under 10 days, so when it is introduced into the body, it has enough time to reach the right cells, but not so long that it concentrates there, shedding too much radioactivity for too long.

The hot cell at the isotope production facility
The hot cell at the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility is used to load and unload targets into a proton beam for irradiation. Credit: Courtesy of Los Alamos National Laboratory.

However, to help actinium cause no harm (or as little as possible), it needs an additional ingredient: something that prompts it to seek out cancerous and unhealthy cells. Recently, researchers have developed FDA-approved treatments that can locate a molecule on the surface of prostate cancer cells and deliver radiation to the problem area.

“When it recognizes a prostate cancer cell, it attaches to it,” Rector says. “And it clings only to those cells.” Similar treatments are now being developed with actinium 225. These targeted drugs could deliver the radioactivity of that isotope right where it’s supposed to. to inflict damage, like a “heat-seeking missile,” says Mitch Ferren, former associate director of commercial operations at the National Isotope Development Center. It is a form of treatment called “alpha directed” therapy.

About a dozen clinical trials have involved or currently involve actinium 225, testing treatments not only for prostate cancer but also for diseases such as leukemia, solid tumors and carcinomas. The initial development of a targeted alpha compound involving actinium 225, back in 2013, “not only provided a new treatment option for prostate cancer, but also demonstrated the technology’s potential for cancer treatment in general,” says Alfred Morgenstern of the European Commission’s Joint Research Centre, one of the few places currently producing actinium 225.

So far the studies look promising, and that promise has a long historical basis. Researchers have known that actinium-225 would likely be useful for cancer treatment for more than 30 years, beginning with the publication of a paper titled “The Feasibility of 255Ac as a source of α particles in radioimmunotherapy” in Nuclear Medicine Communications in 1993. Decades of research followed, but it was only after the compound for targeted treatment was synthesized that practical developments really increased. Seeing that, the DOE stepped in to help increase supply to meet future needs. “Demand has increased significantly and it is extremely important that new production facilities come online soon to mitigate supply shortages,” says Morgenstern.

Right now, labs in Germany, Russia, and Canada make this isotope, but most of Earth’s actinium-225 drips from a supply of thorium-229 in the form of old nuclear waste living at ORNL. As this thorium ages, it decays into an isotope of radium, which then naturally decays into actinium 225. Interestingly, everyone calls this “milking the thorium cow.” But the cow’s flow is low and there is not enough milk for testing, let alone future treatments.

That’s why the DOE started what it calls the Tri-Lab effort (after the triple team of LANL, ORNL and Brookhaven) to build a more golden cow, producing actinium 225 in new ways.

“They started investigating several different alternative pathways,” says Karen Sikes, director of the National Isotope Development Center. But one stood out: shooting protons at targets made of thorium 232. Those protons that crash and stay put create the right type of actinium through a process called spallation. Tri-Lab Effort has worked on the specific infrastructure and techniques to do this, using existing particle accelerators to create the proton beams that are fired. It has worked, as the first batches were processed in 2018. In 2022, Tri-Lab researchers were able to produce more than six times the amount they produced in 2018, although it is likely still a fraction of what the medical industry will eventually produce. It may require. At LANL, early work has begun on a new facility dedicated to producing isotopes such as actinium-225. “This would allow us to dramatically increase the amount we can produce,” says Rector.

“What we are doing now is modern alchemy,” he proclaims. It’s a bit grandiose, but it’s not wrong: the fundamental idea of ​​alchemy is to take an abundant and cheap element and transmute it into something rarer and more valuable. In the old days, that meant pseudoscientific efforts to turn lead into gold using something often called the philosopher’s stone, which supposedly contained within its rock the forces of the universe.

Today that sounds silly. But, Rector says, “we actually think they were right. We can make those transformations. “They just had the wrong magic rock.” The modern magic rock is a particle accelerator that changes the identities of atoms using protons at a rapid rate. “We are harnessing the forces of the universe to transform one element into another,” Rector says.

However, actinium 225 made with this Tri-Lab method has one potential drawback compared to the version made with cow thorium: it is mixed with actinium 227 (which has two more neutrons), which cannot be easily separated. the desired isotope. “The advantage of the spallation process is that the target material, thorium 232, is available in abundance and, in theory, production can be increased more easily,” says Morgenstern. “However, the process requires large and expensive accelerators. And the actinium 225 product is contaminated with long-lived actinium 227, causing handling and waste disposal problems.”

Understanding if and how that impurity affects supply may require different trials. But that is also underway: the FDA accepted to “drug master file” which described the accelerator-based actinium production facilities and processes back in 2020.

When researchers or pharmaceutical companies want actinium 225 for their drugs, their orders can go through the National Isotope Development Center, which is a commercial arm of the DOE.

Some customers, such as buyers of actinium 225, are in the medical industry, but other isotopes are found in atomic clocks, spacecraft, computers, and oil and gas instruments. Instead of competing with the private sector, the center only sells isotopes that the commercial industry does not produce in adequate quantities or that have a production problem that requires filling a gap. “What has certainly been a big effort in recent years is reducing our dependence on foreign supplies, particularly from Russia and Ukraine,” Rector says, “and making sure that the isotopes that we need and that are critical for industries like Semiconductor manufacturing or quantum computing are things we have available in the United States.” Rector makes sure the right amount of the right isotopes are ready when needed, something the alchemists of yesteryear couldn’t accomplish.

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