So, to understand where we are going, let's have a look at the entire life cycle of a radiopharmaceutical dose. Regarding supply chain, usually most of the discussions actually address the challenges of irradiation, soft processing, radiolabeling, logistics. But for the next few minutes, I want to focus really on the first two chains of these supply chains, the mining the ores and the enrichment.
The main challenge we face here is that there is no one-size-fits-all product raw material. As you all know, almost each radionuclide require distinct starting material. This diversity means that industry must maintain a massive, highly-specific inventory of source material, each with its own sourcing hurdles.
So the question is, how does source material needed for radionuclide production, and how are we actually preparing them? So, for that, to illustrate why the nuclear side of supply chain are quite demanding. Let's have a look at two contrasting example of source material. I'll take holmium and ytterbium.
So on one end of the spectrum, we have the ideal scenario, I would say. Natural holmium is mono-isotopic, meaning it consists of nearly 100% holmium-165. So basically, you can put natural holmium into a reactor, and you will get holmium-166, so it's a straight and efficient pass. Unfortunately, in the world of nuclear medicine, holmium is actually an exception and not the rule.
The reality for most radionuclide is far more complex. If you look at ytterbium, for example, for lutetium production, if you pull a sample of natural ytterbium from the ground, what you're getting is a mix of seven different isotopes. You're getting ytterbium-68 at a mere 0.12% that you cannot even see on this chart. You're getting ytterbium-174, up to 32%. But you only care about ytterbium-176.
If you irradiate a natural ytterbium target, what you will get is a mix of very different unwanted isotopes that will contaminate your product, and will be basically unusable in a clinical environment. So you just don't need ytterbium, actually you need ultrapure ytterbium-176, and reach to 99.9%. This has a cost. Basically, a gram of some ytterbium oxide, you can get it for a few tens of bucks on the open market. While on the other hand, a single gram of pure ytterbium-176 can cost up to $30,000.
So, the question is, why is it so difficult or expensive to isolate the right isotopes? Let's look a bit at the physics. I hope many of you in this room had the pleasure to see Christopher's Nolan Oppenheimer, because first, that's a good movie, but more importantly for our discussion today, because it provides the perfect primer for understanding isotopic enrichment.
Because one of the key challenges of the Manhattan Project at that time was essentially the same that we face in nuclear medicine, isotopic separation. Because natural uranium only contained 0.7% of uranium-235, and only this one is facile, so you have to separate it from other isotopes. To solve that, the US actually built different specialized facility in Oak Ridge, Tennessee, experimenting at that time with very, very different enrichment technologies.
They played with gaseous diffusion, thermal diffusion, centrifugation, electromagnetic isotope separation that you may have already seen, the bottom right picture with Calutrons. After the World War II, the immediate need for weapons grade uranium shifted, and actually these very same machines, they were used for stabilized to production, like the Calutrons were used for ytterbium-176 at that time.
So let's now dig a bit about the different technologies that are used today. So nowadays, we rely on three different technologies, I would say, distillation, centrifugation, and electromagnetic separation. So let's briefly look at these three technologies that are used basically to enrich almost any element on the periodic table.
So, starting with distillation. This method is purpose-built for lighter isotopes at the top of the periodic table. The physics is quite simple here. Lighter isotope process, slightly higher vapor pressures, meaning they evaporate more readily than the heavier counterpart.
So, by using these massive fractional decision columns, we can explore those differences to achieve high purity. This is how we produce oxygen-18, for example, from [inaudible 00:05:46]. From a supply chain perspective, there is no real challenge on this side, considering that there's a lot of players, and we are very close to a chemical sector.
So let's move to centrifugation, which is a bit more complex. The first hurdle here is really chemical, because before you can enrich, you must convert your element into a stable gas form. Once in this gaseous state, the physics is quite straightforward. You have the centrifuge that spin at incredible speeds, and the heavier molecules are forced outward, while the lighter ones remain closer to the central axis. That's basically how you do the separation.
But the separation factor for a single machine is relatively low. So to reach high enrichment levels, you have to link hundreds, if not thousands, of these machines altogether. A single group of centrifuge can only produce one specific isotope at a time. So, the industry has to operate on an annual campaign basis, meaning that you're planning your campaign on a yearly basis, one after the other. So it means that you need to understand quite well the demand and its evolution in the future.
This is, again, here a small market, only a few players. Russia is controlling more than 50% of the market right now, with Urenco being just after that, with roughly 30% of the market. Orano now just entered this small club with a new facility launched in 2023.
So, let's switch to the third one, the electromagnetics separation. So how does it work here? A field material is heated to produce an ion flux, which is then accelerated through a high intensity magnetic field. And here, this is the magnetic field that separate the isotope based on their mass, and they are intercepted into individual collectors following this circular pass.
This is great, because this allows to separate multiple isotopes simultaneously, but with relatively low yields, only gram-scale quantities per run. Following the decommissioning of Oak Ridge Calutrons, the same one I mentioned previously, the market had to rely on Russian supply for years, and that was a major risk. Now the situation is a bit better. We see that actually several players have deployed or are developing enrichment capabilities, which is now securing the market.
Before concluded, I wanted to shortly make a focus on actinium-225 and radium-226, its precursor, because this illustrate basically the typical chicken and egg dilemma that we see in this very specific sector. Because radium-226, the precursor for actinium production, hasn't been actually produced for decades. I mean, that was a great radionuclide one century ago, with the first development in nuclear.
But restarting primary radium-226 production will require massive capital investment and complex licensing with very complex facilities. These world players are nowadays hesitant to fund such a move. So, the bottleneck for radium now is quite financial and strategic. So, what I mean is that the question is, will the market's signal will trigger investment in the future, before the legacy material are basically exhausted?
So to conclude, there are different takeaways I would like to highlight. First, the stabilizers are not commodities. They are really essential, because without that, we cannot do anything. There is no one-size-fits-all solution. We use distillation, centrifugation, and electromagnetic enrichment, depending on our needs.
From a cost of goods perspective, this seems to be expensive, but in the end, it's only a few percent of the total price of a radiopharmaceutical. I will now stop here to let my colleagues speak about radionuclides. Thank you.