The UK's Radiopharma Revolution

Cancer is one of the top global killers and is forecast to increase in prevalence over the next ten years. Radiopharmaceutical therapy is a rapidly advancing approach that has the potential to drive game-changing breakthroughs for patients. Demand is increasing, with the number of patients needing radiopharmaceutical treatment expected to exceed global healthcare systems capacity in 2025 and double by 2027. The global radiopharmaceuticals market was worth over $6 billion in 2023 and is projected to grow to over $15 billion by 2032.

Within radiopharmaceuticals, targeted alpha therapy (TAT) could potentially one day replace chemotherapy. It is more targeted, more effective, and has far fewer side effects for patients. TAT uses alpha-emitting radionuclides bound to cancer-targeting molecules to deliver radiation directly into cancer cells. Alpha particles have high linear energy transfer (80-100 keV/µm), meaning that only a small number (~10) are needed to effectively target and destroy cancer cells with minimal damage to healthy tissue. They are also more likely to cause double-strand breaks in DNA, one of the most effective causes of cell death. Numerous drug molecules can be used for radiopharmaceuticals, with a current focus on antibodies, peptides, and small molecules that target proteins only found on cancer cells. The approvals of Lutathera and Pluvicto were hailed as a huge step forward in the field.

Accessing isotopes
 

Access to radiopharmaceutical isotopes is a significant challenge for some countries. In the UK, for example, there are no current production routes, which means that clinical trials and widespread use of TAT within the country are dependent on (and limited by) the import and availability of radionuclides generated abroad.

The number of radionuclides suitable for TAT is small (ca. 11), and by nature, they are required to be “short-lived”. Thus, some of the radionuclides generated abroad cannot be transported in the timescales required before they decay to “unusable” levels of radioactivity. As such, it is vital that countries like the UK can produce their own isotopes to secure a steady supply and provide life-saving medicines to patients.

Harvesting medical radioisotopes requires the desired radioisotope to be present in the source material. Where this is not the case, a method to make the radioisotope is required, typically using an accelerator system or a nuclear reactor. Currently, the UK does not have sovereign capabilities to do this, except for a small number of specific radioisotopes, and the country’s nuclear medicine sector faces significant infrastructure deficiencies:

• Lack of facilities to produce, manage, and administer high-potential isotopes.
• The lowest number of CT scanners among 23 major economies, with approximately nine scanners per million people, compared to the Organisation for Economic Co-operation and Development average of 15 scanners per million people.
• Significant investment is needed in gamma cameras and PET/CT scanners to facilitate advances in nuclear medicine.
• Investing in technologies like PET (Positron Emission Tomography) is crucial for early and accurate disease detection, better patient outcomes and more efficient healthcare delivery.

Developing this infrastructure would unlock significant research opportunities, enable more clinical trials, and make radiopharmaceutical development more accessible and achievable.

Pushing radiopharmaceuticals in the UK
 

Outcomes for cancer patients in the UK are lagging significantly behind comparator countries, with one-year and five-year cancer survival estimates lower for all but two major cancer groups. One of the key underlying reasons for this has been a market failure to invest in the infrastructure necessary to support early pre-clinical and clinical trials into new radiopharmaceutical treatments.

Medicines Discovery Catapult (MDC) and United Kingdom National Nuclear Laboratory (UKNNL) have established pedigrees in their respective areas. Over the last few years, we have built a strong working relationship and collaborated on several programs.

MDC is a national life sciences service that helps turn drug discovery into impactful and commercial breakthroughs. We operate a preclinical facility, with world-class radiochemistry capabilities and a translational suite of imaging technologies.

UKNNL enables the supply of vital radionuclides for the UK. For the last eight years, it has been developing processes to extract and purify potential TAT radionuclides from nuclear waste. A promising route, which has been developed to significant maturity, is extracting lead-212 (via its parent radionuclide thorium-228) from legacy nuclear material that has been used to power around a sixth of the UK’s electricity in one of the nation’s nuclear power plants. Once the fuel is removed from the reactor, it still retains energy, minerals, and radioactivity in the form of isotopes. Some of these isotopes are unstable, emitting small amounts of radiation as they follow the natural decay process.

Lead-212 has a half-life of around 11 hours before it becomes stable, making it ideal for use in radiotherapies. It reduces long-term radiation exposure for patients and is also compatible with a variety of targeting molecules for precision oncology therapy. Radiopharmaceutical therapies are injected into the body and bind to specific molecules on the surface of cancer cells. Once bound, they deliver cell-killing doses of radiation to the cancer.

The process of chemically separating radioisotopes from spent nuclear material has been successfully established at lab bench scale. Current work is ongoing to scale this up; however, this would still only produce lead-212 in very small quantities and would not be sufficient to provide it to researchers in the quantities needed for extended clinical trials.

MDC and UKNNL have combined their expertise and collaborated to secure funding from Innovate UK’s Sustainable Medicines Manufacturing Innovation Programme. Together, we will finalize the case for further scale up of the harvesting of precision nuclear medicines from the UK’s legacy nuclear material.

Working in partnership, we will explore potential options for making the nuclear material available to researchers and drug development companies. The long-term aim is to enable commercial production and routine use within the National Health Service for the benefit of patients and the development of a new community.

Our immediate focus is on building a consortium that will provide the UK with access to a local supply of radioisotopes. By bringing together the supply chain with regulators to discuss the challenges, particularly those associated with logistics, waste and safety, we will leverage cross-sector expertise from two highly regulated sectors, including industry, national regulators, SMEs, academia and clinical, to map the challenges and propose solutions.

We aim to establish a reliable, UK-based supply chain for lead-212 production to ensure the future availability of radiopharmaceuticals for clinical trials, research, and commercial applications.

The benefits
 

Radiopharmaceutical therapies offer a transformative opportunity for cancer treatment and research, but a national supply of isotopes is important. The multi-disciplinary consortium-based approach spearheaded by MDC and UKNNL will maximize opportunities for innovation and provide a unique route to provide security of supply and confidence in delivery.

Radiopharmaceutical therapy has the potential for use in a wide range of cancer types, including more common cancers, and the landscape is expected to experience significant growth. Added to this, the number of patients expected to need nuclear medicine is expected to increase over the next decade, with demand for radiopharmaceutical therapies projected to exceed global healthcare systems capacity by 2025 and double by 2027. Creating these new targeted treatments from nuclear waste could transform patient outcomes.