How compact neutron sources are revolutionizing cancer care: Q&A with Noah Smick of Neutron Therapeutics


Aviko product collage including various frozen foods

Aviko recently spoke with Neutron Therapeutics’ president, Noah Smick, Ph.D., about his company and the technology and physics that powers its products.

While boron neutron capture therapy (BNCT) has been a promising cancer radiotherapy for decades, it has only recently become a viable clinical modality. In addition to major developments in drug delivery and pharmacology, the design of compact accelerator-based, in-hospital sources of safe neutrons can today replace previously required nuclear reactors and enable treatment.

Among the industry leaders in providing compact neutron sources is Aviko partner Neutron Therapeutics, a medical equipment company based in Danvers, Mass., and Helsinki, Finland. Since 2015, Neutron Therapeutics has been working to bring BNCT out of the realm of medical research and transform it into a widely available first-line cancer therapy. Its flagship device, the nuBeam® suite, is a complete BNCT solution. nuBeam is also the only device that meets the TECDOC 1223 recommendations from the IAEA for BNCT Clinical Use.

IAEA Guidelines for BNCT Clinical Use

IAEA table depicting nuclear energy statistics

How did you get involved in developing accelerator-based neutron sources?

We started developing accelerators for the solar industry in 2010. At that time, we were using them to create thin films of silicon by implanting protons at a precise depth beneath the surface, then peeling off the micron-thick layers. The process made perfectly viable solar cells using far less silicon.

We did a lot of interesting things in this space, like exfoliating sapphire and silicon carbide and various other materials for different applications. During that time, in the early 2010s, we also became aware of BNCT and realized that our technology could be used in that domain as well. Neutron Therapeutics was subsequently born in 2015.

That was an interesting time for BNCT, right?

Absolutely. Japan had become the center of gravity for BNCT research decades earlier, but in 2011, after the Fukushima nuclear disaster, Japan joined many other countries around the world shutting down their research reactors. A similar trend was taking place in Finland, another center for BNCT research, though for different reasons. Both countries were generating great clinical results, but without research reactors, they couldn’t do BNCT-related studies.

The team at Neutron Therapeutics knew we could contribute by generating high-intensity neutron beams and bringing this capability into a hospital environment. We started at the University of Osaka, in Japan, and the University of Helsinki Hospital, in Finland. By then we were also thinking about the bigger problem of making a medical device for BNCT — not just the accelerator, but the target and the other technologies needed to support BNCT as a modality.

You refer to the “problem” of making a medical device for BNCT. What problem were you trying to solve?

The problem was one of power. Taking a very powerful proton beam and pointing it at a delicate substrate — which is a target made of lithium — can be problematic. Lithium melts easily and it’s very reactive.

This is a similar issue to what exists in the semiconductor and solar cell production industries. As we had learned in our previous work for the solar industry, we had many technology solutions that were directly applicable to BNCT.

Why is the lithium reaction the preferred target for BNCT, given the material’s challenging traits?

The nuBeam system utilizes lithium within its target system. Lithium is a difficult engineering material, as you note. You can’t build with it, it has a very low melting temperature, it’s soft, and it has poor thermal conductivity. It’s also chemically reactive, meaning it reacts with all sorts of things. It’s easy to understand why people are hesitant to use it as a major component of their BNCT system.

But we took those challenges and tackled them head on. Why? Because the alternative is to use a higher energy neutron source, which makes high multi-MeV neutrons. Those are bad for BNCT. They’re difficult to slow down and filter out of a beam, and they are biologically hazardous.

The whole point of BNCT is that the neutron beam itself should be benign. That means you don’t want any fast neutrons in it. The more something is exposed to fast neutrons, the more radioactive it becomes. For all these reasons, we would prefer to use a lithium reaction.

Additionally, the energetic purity of the neutron beam in BNCT is best for reactions whose yield ramps up very quickly above the reaction threshold energy. This allows you to achieve sufficient neutron intensity without excessive neutron energy. The lithium reaction is by far the best from this perspective — it turns on like a light bulb.

But we did have to overcome significant engineering challenges to arrive at the current nuBeam solution.

Can you elaborate on how you solved the engineering challenges associated with lithium?

The core innovation around our device is the ability to maintain the temperature of the target, in this case, lithium. The typical approach that people take is to try and aggressively cool the target by throwing many costly heat removal technologies at it which can only marginally improve power handling.

We took a different approach altogether, one that is very familiar to those who work within the semiconductor industry. Instead of trying to manage unreasonable power loads in very small areas, we chose to make our target large and to spread the power over a big area.

The way we do that is we have a large disc with 16 individual lithium coated targets that look like flower petals. This disc spins very fast in front of the proton beam. That’s really the core of our technology — the rotating target — which we’ve patented and developed.

What else is happening inside your machine?

When you have a nuclear reaction and the proton beam hits the lithium target, neutrons are flung off in all directions. Neutrons are, by their nature, extremely difficult to corral. They have no charge and can’t be affected by magnetic fields. They just go wherever they want. The only way to exert influence on them is by putting materials in front of them and allowing them to bounce off the nucleus of an atom in that material.

The goal of generating a neutron beam for BNCT is to transform a high energy, omni-directional neutron source into a lower energy, collimated neutron source, with all the neutrons going in the same direction coming out of a prescribed aperture.

The first and most important component we use is called a moderator. Its purpose is to slow the neutrons down to the appropriate energy. Most BNCT manufacturers have settled on a material called magnesium fluoride for the moderator.

The next required component is called a neutron reflector. Its purpose is to have neutrons bounce off it with minimal impact on their energy, and to do so without absorbing them. The most common material for that is lead.

The final tool you use is a neutron absorber. In BNCT, the materials that are typically used for that are lithium and boron. These materials have high neutron absorption cross sections and minimal reaction products.

Once you’ve done the best you can to get the beam going in the direction you want, with the energy level that you want, you then need to surround the whole assembly with neutron and gamma shielding material to prevent radiation outside the beam from reaching the patient or activating things in the room. It’s really a very complex piece of equipment that took an enormous amount of technical engineering and problem solving to create.

Nubeam logo on a blue background

What kind of protections are there for the technicians who administer the therapy?

nuBeam generates low-energy neutrons and limits the number of fast neutrons, which reduces activation. We also carefully selected the materials we use to make sure that they’re not activated by the low-energy neutrons. Protecting the technicians was an important design goal, and we’re quite proud of the safety levels we have achieved. The entire system was also designed with an eye towards serviceability.

Finally, what might a patient receiving BNCT treatment with nuBeam expect?

Undergoing cancer treatment is, by all accounts, a difficult experience. Patients enter into different treatment regimens and it’s not always fully explained to them what’s going on. It’s a lot to manage on top of feeling ill. We wanted to do everything we could to improve the patient experience.

One of the ways we do that is by ensuring there’s a human connection, a human presence. We didn’t want patients to be in a treatment room all alone, told that it’s simply too dangerous for anyone else to go. Because of our machine’s design, it’s safe for technicians to be there alongside the patient right up to the moment of treatment. We are also working with Leo Cancer Care to integrate upright patient positioning into future iterations of the nuBeam. Leo’s solutions allow patients to feel comfortable and more engaged with their technicians.

The other factor with BNCT is that it’s often delivered in a single session, ensuring that treatment is as efficient as possible. It’s much less of a burden on the patient to go in once than to go in for dozens of treatments which is common with other forms of radiotherapy such as proton therapy. We think BNCT is a transformative radiotherapy modality for these reasons.