Targeted Alpha Therapy (TAT) is a promising cancer treatment in nuclear medicine, but the supply of alpha-emitting radionuclides – which the treatment relies on – is very limited. A lack of alpha-emitting radionuclides in the UK is preventing research and clinical trials, and inhibiting future treatments. However, the UK has accumulated legacy nuclear materials from which the necessary radionuclides could be extracted, says Samantha Ree, 1851 Royal Commission Industrial Fellow.
Radionuclide medicine is a field that uses small amounts of radiopharmaceuticals to diagnose and treat various medical conditions. In the UK, approximately 700,000 medical procedures involving radionuclides are performed each year.
These procedures depend upon the decay of atoms with a nucleus that has excess nuclear energy making them unstable. To become stable, the radionuclide expels this extra energy by emitting radiation (e.g., alpha, beta and gamma radiation). These radioactive emissions allow either (i) the drugs to be detected in the body for diagnosis or (ii) to be used for therapy.
Tc-99m is the most extensively used radionuclide and is employed for diagnostic purposes. Therapeutics use in this area is much smaller, usually focused on treating thyroid cancer and bone metastases, with less than 5,000 procedures occurring annually in the UK.
Targeted radionuclide therapy (TRNT) is a promising oncology treatment that relies on a chemical construct capable of binding selectively to specific target sites (a receptor existing on the targeted cancer cells surface). This construct comprises the cancer seeking agent, a linking molecule and a chemical chelator bound to a radionuclide.
One type of TRNT is Targeted Alpha Therapy (TAT), which uses alpha-emitting radionuclides chemically attached to a targeting moiety, with the radiopharmaceutical accumulating at disease sites. The alpha emissions from these radiopharmaceuticals have a high linear energy transfer (LET), which deposits a high amount of ionising energy over a short distance. This high LET limits damage to only the cancer cells in which they locate, protecting the surrounding healthy tissue.
The high LET also means that the radionuclides will cause double-strand DNA breaks and cell death in the cancer cells. There are only a small number of radionuclides that have the radioactive decay properties useful for TAT.
TAT research and clinical trials rely on a supply of suitable radionuclides, and is currently very limited, especially in the UK. International production requires tightly controlled starting materials. The production of radiotherapeutics has been the domain of small specialist firms with limited manufacturing operations. Furthermore, radionuclides for TAT are short-lived and undergo rapid radioactive decay, which means they cannot be stored for long periods.
To fully realise the potential for nuclear medicine, we must look to create a reliable and large-scale supply of radionuclides, so that hospitals have access to a powerful therapeutic tool for diagnosing and treating diseases such as cancer.
The National Nuclear Laboratory (NNL) utilises carefully stored nuclear material that can yield Pb-212 (parent to Bi-212, an alpha emitter), Ra-224 (loaded into a “generator”, where it too decays to Pb-212/Bi-212), Th-228 (loaded into a “generator”, where it decays to Pb-212/Bi-212), three radionuclides of interest for TAT.
NNL, the University of Manchester and the Royal Commission of the Exhibition 1851 are supporting research related to recovering and purifying these radionuclides. The harvesting of Pb-212 and Ra-224 have already been proven at a small-scale and require complex chemical separation and purification of nuclear material.
This builds on NNL’s world-leading capability in this area and its plans to scale the production route to remove the significant supply constraints currently faced by hospitals. As part of this project, I will be focussing on the optimisation of the process associated to the harvesting of Pb-212 and Ra-224 to improve the separation technique, this includes scaling-up the current process to allow for secondary purification trials (required to increase the purity of the Pb-212 and Ra-224 products).
This will help finalise the flowsheet for the process. With a reliable and large-scale supply of radionuclides, hospitals can implement nuclear medicine approaches to treat diseases like cancer more effectively and make a tangible difference for patients using the characteristics of radioactivity.
Samantha graduated with a Master’s degree in Chemistry at Newcastle University before joining the National Nuclear Laboratory in 2017 on the Technical Graduate Programme. Since then, Samantha has worked in the Chemical and Process modelling team and the Waste and Residue processing team, where she is now undertaking her PhD as part of her Industrial Fellowship with the Royal Commission of 1851, in partnership with the University of Manchester.
