Ionising radiation plays an important role in the medical world, even if it’s not as widely discussed as other fields. From well-known radiotherapy treatments and brachytherapy for cancer to advanced imaging techniques such as positron emission tomography (PET) scanning, nuclear medicine has a wide range of applications in medical treatment and diagnostics.
Scientists believe there’s more to discover in the field of nuclear medicine, but the challenges involved in securing a steady supply of radioactive isotopes that are of potential medical interest has been a restraining factor on research. The ISOLDE radioactive ion beam facility at European nuclear research facility CERN has been used to explore the use of radioisotopes in medicine since the 1970s, but limited access to ion beam experiment time and a lack of infrastructure to handle the radioactive resources needed for research has been an ongoing issue.
Thus, the CERN-MEDICIS project was born. The programme was launched in 2010 as a collaboration between CERN, the University of Leuven and a number of other academic and healthcare partners. The project aims to use ‘beam dumps’ that would otherwise be wasted in primary experiments as a source of new isotopes for medicine.
Non-resectable pancreatic and brain cancer – particularly deadly forms of the disease, which are often asymptomatic until the advanced stages – have been highlighted as initial targets for new therapies and diagnostic tools. The MEDICIS building at CERN began construction in 2013 and completed in June this year (standing next to ISOLDE), with a range of research organisations joining the project in the intervening years.
One such addition to the CERN-MEDICIS team was the National Physical Laboratory (NPL), the UK’s national measurement institute, which has been involved in technological developments ranging from Turing’s first automatic computing engine to the packet switching concept that underpinned the invention of the World Wide Web. NPL is providing measurement support for the project, setting standards for the production and replication of rare isotopes that should help clear barriers to clinical testing of any rare isotopes produced.
Dr Andrew Robinson of NPL’s medical radiation physics team, who is leading the lab’s work on the CERN-MEDICIS programme, discusses the project, the intricacies of NPL’s role and the potential impacts for personalised diagnostics and therapeutics of the future.
Chris Lo: How did the CERN-MEDICIS project get started?
Dr Andrew Robinson: The idea of the CERN-MEDICIS project is to be able to use the capabilities that they have there in terms of their accelerators and their fundamental nuclear physics research programme, to be able to use that to produce isotopes that are of potential interest in terms of radiopharmaceuticals.
It’s the sort of work that had been going on at CERN for a reasonable amount of time. People were requesting beam time at the ISOLDE facility [CERN’s radioactive ion beam facility] just to collect these interesting isotopes for medical applications and also for a lot of solid-state materials work as well. So there’s a demand for these rare isotopes that you can make at CERN.
I don’t know how much you’ve seen of the facility, but the basic idea is you have a large target and you put the high-energy proton beam on to that, and because it’s a very high-energy proton beam, about 80% or so of the beam goes right through the target and stops on the wall – a beam dump. The idea, then, was you could take that 80% that’s not stopped, you could put another target there and you could use that target to produce stuff off-line, effectively. So that’s the idea of the MEDICIS project, using a second target station so rather than having to take primary beam time on the main target, you have a second target behind it. So anytime there’s an experiment, you can be making various isotopes.
CL: How are medical isotopes produced?
AR: There are two main production mechanisms for medical isotopes, depending on the isotope. It’s either cyclotron production – so for short-lived things like 18F [fluorine-18] for PET imaging, that’s made in cyclotron production. There are a number of commercial cyclotron facilities around the UK, and they make these short-lived isotopes. Then, a lot of the other isotopes are made in nuclear reactors, so they’re by-products of the nuclear industry. So they very much rely on having a reactor working.
So really, MEDICIS is about getting small amounts of any isotope that people are interested in as research fields to accelerate the uptake of these new pharmaceuticals.
It’s all very much led by the pharmaceutical side of it, which as a physicist is the squishy bit that I don’t have very much to do with! But it’s very much about matching up the chemistry for a trace that will work in the body, and then that determines the chemistry of the radionuclide that you can attach to that. As a physicist you might say, ‘Oh, that’s a really good isotope, we should use that.’ And then the chemist says, ‘You can’t put that in a human,’ or, ‘There’s no way I can attach that to the molecule that I’m interested in.’
CL: Could you tell me more about NPL’s role in CERN-MEDICIS?
AR: The NPL involvement is to provide measurement support for what they’re doing with the MEDICIS project. As part of our nuclear medicine work, we provide primary standards of radioactivity for all sorts of medical isotopes. The way that measurement is made is on some form of calibrator in the hospital. Those calibrators are traced back to a primary standard of radioactivity, and that’s what the national measurement institutes develop and check against each other. So before you can administer a pharmaceutical to someone, it has to be traceable back to one of these standards.
For these exotic isotopes there often isn’t a primary standard, because the first thing you need for a primary standard is some of the isotope to make the measurements on. So that’s where we’ve come in, in that we’ve been getting shipments of some of these isotopes from CERN, they’ve been sent to NPL as part of their run, and then we can do the primary standardisations.
That means in the future, other research sites and clinical sites can actually determine the amount of isotope on their site, traceable back to us. If you want to manufacture a radiopharmaceutical to GMP [good manufacturing practice], you have to have these primary standards to show that you understand the activity. That’s really where the international measurement system underpins that. So if we can get it done now and make those standards available right from the start of the pre-clinical work, it removes that barrier to getting them into humans later on.
CL: Has the project identified areas of particular therapeutic or diagnostic potential for the future?
AR: The isotopes that are of particular interest at the moment [make up] this terbium theranostic quartet – that’s what they’re calling it. That basically means you’ve got four different isotopes of terbium, so the same element but with different mass numbers. Each one of those has different, useful properties. You have one which gives you an alpha emitter, so you can provide therapeutic effects. You have one that gives you gamma rays, which can be used for SPECT [single photon emission computed tomography], so you can look at where you’ve treated, as well as giving the treatment. There’s one that gives you betas so you can do PET [positron emission tomography] imaging, and there’s a fourth one that gives you therapeutic betas.
So it’s really this idea of combining the therapy and the diagnostics together. What typically happens now with a lot of administrations is you’ll use a diagnostic imaging agent to get an idea of what the uptake would be in the patient and try to tailor the therapy to that patient. And then you’ll treat the patient with different isotope. Often, you’ll find that the diagnostic tracer and the therapeutic agent behave slightly differently.
So although that’s fine for ensuring the safety of the patient and you can have a reasonable idea of what’s happening, if you really want to tailor it to that specific individual, if you can have something where your diagnostic agent is identical to your therapeutic agent, and perhaps you’re even doing diagnostic imaging at the same time, so you could perhaps use a mix of these, then that really gives you the next level of personalised medicine. You can tailor that treatment to the individual patient; you can assess how well the patient is responding and make sure you leave open the opportunity for them to have future treatments as they come online. You ensure that you’re giving an optimal amount of radiation to each patient.
That obviously comes with potential cost savings, as well. Instead of treating all patients as the same but with different weights, which is an approach that can be taken now – again, absolutely fine from a patient safety point of view – but if you can really start to look at what is the uptake in this specific patient, in this specific kidney, at this stage of their disease, and then really tailor the treatment to that, there’s a lot of benefit that comes from it.
CL: Does the project have a broad roadmap for developing over the next few years?
AR: The facility came online in June; there will be some more development as they bring more isotope separation techniques over to MEDICIS, and that’s going to ramp up over the next year or so.
The longer-term goal, now that the facility is there, is that anytime there is proton beam being used, going through to the ISOLDE system, they can use that 80% of it that is going through the target, so it doesn’t matter what the experiment in front of it is. Previously, they were scheduling specific experimental time, and I think the fact that they got the experimental time to do this radiopharmaceutical production shows the importance of it at CERN, and the fact that they’ve then taken that on to, ‘Why don’t we have the ability to do this all the time?’ That shows that this is something that’s important and it’s been recognised at CERN.
CL: Could Brexit throw up challenges for NPL’s involvement in the project, or your level of access to these kinds of projects?
AR: I think all science, by its very nature, is a collaboration. At this level, science is an international collaboration, and I imagine that’s going to continue, whatever happens with Brexit. As to how much access we have, I’m not sure that I can really speak to that. I think if you want the science to continue, the collaboration has to continue.