Neutron Generators

The Roles of Radiation, Neutrons, and N-Ray in Medicine

By June 12, 2019January 29th, 2020No Comments

Radiation is often thought of as dangerous and unhealthy. It is, of course, when it’s improperly used, and history has done a very good job of showing us what improper use looks like. Thanks to HBO’s chilling new miniseries Chernobyl, which recently wrapped up its five-episode run, and its unnerving commitment to detail and accuracy (for the most part), the greatest dangers posed by radiation run amok and misused nuclear technology have once again been brought to the forefront of public consciousness.

However, as important as it is to understand what happens when the worst happens (and Chernobyl was, by far, the worst of the worst), it’s also important to keep in mind just how powerful of a force radiation is for good in the world when it is not used carelessly. When radiation and radiation-emitting substances are used properly by doctors who understand and know how to minimize the health risks, their applications are indispensable in cancer treatment therapies and medical diagnostic imaging.

The History of Healing: Medicine Born of Poison

Rod of Asclepius, internationally-recognized symbol of many professional medical organizationsAs scary as the effects of radiation overexposure are, radioactive substances are in good company in the world of medicine. Throughout history, medicine has been developed from poisonous plants and venomous animals. The same venom in a rattlesnake’s bite that turns your blood into a thick red sludge is part of an anti-clotting drug. The horrifically-addictive opium poppy, which wreaked havoc through China and sparked two wars against the British Empire in the 19th century, became the key ingredient in morphine. The poison in the leaves of foxglove, which can cause an irregular heartbeat, is used in Digoxin to treat people with heart failure. Even arsenic has medicinal uses.

In a manner of speaking, all medicine begins as poison that kills whatever is wrong with you faster than it would kill the rest of you. It’s all a matter of using it carefully and prudently. There is a reason why the symbol of the Greek god Asclepius, the god of healing and medicine, is a serpent wrapped around a staff (a symbol still used worldwide by the majority of professional medical organizations to this day).

Radiation: A Journey from Miracle Cure to Health Hazard to Lifesaving Medical Tool

Early 20th century physicians used little-understood at the time radiation to treat illnesses such as tuberculosis

Early 20th century physicians used little-understood at the time radiation to treat illnesses such as tuberculosis

Radiation therapy as a treatment for cancer blossomed out of the discoveries of X-rays by Wilhelm Röntgen and of radium and polonium by Marie Curie, although it had a rocky start. Since the dangers of radiation were not well-understood, the border between the effective use of radiation and dangerous misuse was wide and fuzzy for many decades.

On top of that, people entranced and intrigued by the glow emitted by such elements exposed themselves to terrifying amounts of radiation. Snake oil salesmen and quacks used radioactive substances such as radium and radon as ingredients in so-called “cure-all” powders, salves, tonics, and even toothpaste. Much of our understanding of the hazards of radiation stemmed from the very public discovery of what happened when radioactive materials were misused.

In the early 20th century, when radium was used to make self-luminous paint for watch dials and other glow-in-the-dark products, the factory workers (mainly women) were exposed to dangerous levels of radioactivity. Some of the workers, assured by their superiors that the radium paint was perfectly safe, would even apply the paint to their fingernails, faces, and teeth to add a haunting and fashionable glow to their makeup. After all, why would their boss lie to them?

Of course, the factory workers became severely ill. After a years-long struggle for justice against fierce opposition, the “Radium Girls,” as they became known by the media, won compensation for their medical and dental bills. In the process, their struggle became a pivotal moment in the history of labor rights. On top of that, the Radium Girls’ crusade made people more aware that radiation was not simply a benign substance and that its misuse had severe, occasionally horrific, consequences.

Radiation, the world soon discovered, was not a power to be wielded irresponsibly. Eben Byers, a high-profile industrialist who famously guzzled radium-laced water and proudly promoted its health benefits, died in 1932 from radiation poisoning when his jaw fell off. This put an end to most radiation quackery, although some snake oil salesmen kept peddling their wares well into the atomic age.

However, radiation was not without its legitimate benefits. Over the decades and through careful, prudent, and methodical study, medical scientists learned how to use safe, controlled doses of radiation to destroy cancer cells, and how to apply different types of radiation that were better suited for certain tasks.

Upon their discovery, X-rays were all but immediately put to use to see deeper into the human body than had ever been possible before; greater understanding of the science behind radiation allowed medical imaging to dive to ever greater depths. Radioactive isotopes that could be safely ingested or injected into a patient’s bloodstream were the foundational building blocks that made medical imaging such as SPECT scanning and PET scanning possible.

Medical Isotopes: How Phoenix and SHINE Fill a Pressing Need

A patient having a SPECT scan performed

A patient having a SPECT scan performed

Medical radioisotopes are used tens of thousands of times every day in hospitals all over the world.

Radioactive materials decay over time. The amount of time it takes for one-half of a given amount of material to break down into another, less radioactive material is called its “half-life.” Some elements have extremely long half-lives. Radium, one of the first radioactive elements discovered, has a half-life of 1,500 years. Other radioactive elements, especially the isotopes used in medical imaging, have extremely short half-lives on the order of hours or even minutes.

For diagnostic imaging, hospitals use a solution of isotopes such as technetium-99m or fluorine-18. Technetium-99m only has a half-life of six hours, so after six hours, half of it will have decayed and become useless. After twelve hours, you’re left with a quarter of the original amount, then one-eighth after eighteen hours, one-sixteenth after twenty-four hours, and so on. Fluorine-18, an isotope critical for PET scans, has an even shorter half-life of less than two hours.

In other words, it’s impossible to hoard or stockpile these medical isotopes. The only way to have any of it on hand at your hospital is to create it from a longer-lived isotope onsite, and once you’ve created it, it’s a race against the clock to make sure it gets used while it still works!

Medical establishments create these short-lived isotopes by processing them from another isotope, molybdenum-99. Moly-99 is a much more long-lived isotope than technetium-99m or fluorine-18… with a half-life of sixty-six hours. This longer half-life is just long enough that hospitals can order appreciable amounts of the isotope from their suppliers and not lose too much of it in transit. However, like technetium-99m, it still can’t be stockpiled for future use.

The Problem with Moly-99

Molybdenum-99 is used in over forty million medical imaging procedures worldwide each year, mostly for the diagnosis of heart disease and cancer using methods such as myocardial perfusion scans and bone scans. The issue with moly-99, though, is that even though it’s the most widely-used and widely-needed medical isotope in the world, there are very few places capable of producing it.

Today, molybdenum-99 is produced within nuclear reactors. When a neutron collides with an atom of uranium, the uranium undergoes fission and splits into a cornucopia of smaller elements and extra neutrons (which go on to interact with other uranium atoms and cause more fission reactions). In reactors, for every fission reaction, a neutron is produced that can cause another fission reaction in nearby uranium atoms, which release more neutrons, which produce more reactions, and so on until the reactor reaches a state of equilibrium.

When you shoot neutrons at uranium, molybdenum-99 only makes up roughly six percent of the end products. Other elements and isotopes make up the other 94%, some of which also have uses (albeit limited) in medicine. Using chemical separation, the moly is separated from the rest of the elements, purified, and shipped to hospitals to become technetium-99m.

There are only six major moly-99 producing reactors in the world, all of which are government-owned, and none of them are in North America—the last major producer in the western hemisphere shut down in 2018.

The MIT nuclear research reactor is one of only a handful of research reactors in the United States, none of which produce molybdenum-99

The MIT nuclear research reactor is one of only a handful of research reactors in the United States, none of which produce molybdenum-99

If this sounds to you like a precarious situation—a handful of aging reactors serving every single country in the world’s needs for an isotope necessary for lifesaving medical procedures—you’re right. The supply chain for moly-99 is all too easily disrupted. Abrupt and unplanned reactor shutdowns (temporary or permanent), delays at the airports, and other issues lead to worldwide shortages.

Each hour that passes, around 1% of the total moly-99 you have on hand decays into useless material. When a hospital in the US orders moly-99 from a producer in Australia, about 40% of the moly-99 ordered decays in transit. This means, of course, that hospitals and other medical facilities in need of moly-99 must over-provision and order much more of the isotope than what they require just to make sure they get enough useful material once it arrives at the hospital.

The Solution: Homegrown Moly-99 Production, Thanks to SHINE

What if there was a better way for hospitals in the US to acquire molybdenum-99? What if there were more facilities creating moly-99 that were closer to home and could deliver isotopes more cheaply and quickly? What if hospitals in the US didn’t have to worry about nearly half of the isotopes they buy decaying in transit?

The laws of physics can’t be changed, of course, and there’s nothing anybody can do to make the half-life of moly-99 longer. But as it turns out, you don’t need a nuclear reactor on the other side of the world to create moly-99. All you need is an accelerator-based neutron generator—just like the ones we build here at Phoenix, LLC.

Headquartered in Janesville, Wisconsin, SHINE Medical Technologies was founded in 2010 with the goal to ameliorate the too-common shortages of moly-99 that rattle the medical industry worldwide. SHINE’s medical isotope production capability comes in part from the advances Phoenix, LLC has made in compact, practical neutron generators.

What makes SHINE’s technique for creating medical isotopes different from the norm?

SHINE founder and CEO Greg Piefer poses in front of a Phoenix neutron generator being installed in SHINE’s Janesville facility

SHINE founder and CEO Greg Piefer poses in front of a Phoenix neutron generator being installed in SHINE’s Janesville facility

For starters, there’s no nuclear reactor involved. Instead, a (relatively) lightweight, compact linear accelerator designed and manufactured by Phoenix’s engineers produce the neutrons, which pass through a tank of low-enriched uranium dissolved in water and produce the necessary fission reactions.

Out of all the isotopes of uranium, U-235 is the most conducive to nuclear fission. Historically, producers of moly-99 have used highly enriched uranium (HEU), i.e. uranium that is 20% or more U-235, in their reactors. HEU is difficult to procure, transport, and use because if it fell into the wrong hands, it could be used to build a nuclear weapon. Low-enriched uranium, on the other hand, cannot.

Within the past decade, legislative and market pressures around the world have been pushing makers of moly-99 to switch from HEU to low-enriched uranium (LEU). As the name suggests, LEU is less than 20% U-235, but still contains enough U-235 for practical applications. Because LEU can’t be used in nuclear weapons, there are fewer regulatory burdens surrounding its use.

With new ground broken on its new facility in Janesville, SHINE is rapidly transitioning from its design phase to manufacturing. When this facility comes online, its eight Phoenix-sourced neutron generators will enable SHINE to produce over half of the US demand and one-third of the global demand for moly-99, reducing the burden on aging overseas reactors and assuaging painful medical isotope shortages. Earlier in 2019, Phoenix and SHINE conducted a milestone 5.5-day joint test of the high-flux neutron generator that will drive SHINE’s medical isotope production system which yielded unprecedented neutron output and reliability, and then followed it up with a world-record-breaking joint test which yielded the highest sustained neutron output from a fusion neutron source in human history, beating the previous record holders by over 25%.

Neutron Capture Therapy: Shooting Neutrons at Cancer

Another exciting possible use of Phoenix’s neutron generators in medicine lies in the role neutron radiation can play in cancer therapy. Elements that react strongly to neutron radiation, such as boron and gadolinium, can be used to target tumors and help doctors treat cancer patients more effectively with fewer side effects.

How Boron Neutron Capture Therapy Works

The free neutrons produced by our generators can zap tumors and kill the cancerous cells, leaving healthy cells untouched, when utilized in a process called boron neutron capture therapy.

Boron neutron capture therapy involves taking molecules that have an affinity for cancer cells and sticking boron atoms onto them, then injecting the solution into the patient’s body. The boron will fill the tumor. Then, a beam of neutron radiation is shot at the tumor—or, more specifically, at all the boron permeating it.

Boron has a high neutron absorption rate, which means that when a stray neutron collides with a boron atom, it will gobble up the neutron. The boron atom emits an alpha particle in a process dubbed “alpha decay,” which produces alpha radiation.

Alpha radiation is ionizing radiation—the kind that destroys cells. In fact, among the many types of radiation, alpha radiation is one of the most destructive to life, even though it doesn’t travel very far and can’t penetrate skin (everything underneath your skin, though, is a different story—which is why alpha particles are generally only a danger if you ingest something that emits them). However, in this case, that’s good! After all, the whole point is to kill the cancer cells, and it stands to reason that you need something fairly deadly to accomplish that.

When a neutron collides with a boron atom within the patient’s tumor, the alpha particle emitted in the collision travels through the cancer cell adjacent to it, breaking its DNA and rendering it unable to replicate itself. Since alpha particles don’t travel very far, they cease to become a threat after busting through a couple tumor cells. Healthy cells adjacent to the tumor, aside from a little collateral damage, will be left unscathed.

Boron neutron capture therapy is a technique still in the early stages of development. One of the biggest issue holding neutron capture therapy back is the matter of sourcing the neutrons used. Research and test reactors maintained by universities are the most plentiful source of neutron radiation today, but come with a whole host of issues, especially for medical use. As the name suggests, research reactors are good for research, but difficult to bring patients to for treatment.

Accelerator-based, reactor-less neutron sources such as Phoenix’s own neutron generators are a key to furthering the development of neutron capture therapy as a promising treatment for cancer patients.

From the day the very first ancient human discovered that eating a small enough bit of a poisonous plant made them feel better instead of worse, the evolution of medicine has been about refining even the deadliest substances into cures. Once we discovered radiation, it took a long time to fully understand its properties—both the benefits it offered and the threats it posed—and work out how to use it for effective medical treatments, much like any other dangerous substance we wrangled into medicine.

Radiotherapy and medical radiography took a long and winding road through the 20th century to arrive at the point where they became the well-established and widely-used medical practices we know them as today. Newer treatments like neutron capture therapy have years to go as well while the technology that enables them develops; at Phoenix, we’re proud to serve customers like SHINE that help us further advance medicine and nuclear technology’s role in hospital settings.