Introduction: Pioneering nuclear research for nuclear medical applications

Since its establishment in 1952, the Belgian Nuclear Research Centre (SCK CEN) has been at the forefront of nuclear research and the advancement of nuclear medical applications.

SCK CEN’s research strength lies in its integrated ecosystem, which unites a diverse array of scientific disciplines within its Institute of Nuclear Medical Applications (NMA). This collaborative environment plays a pivotal role in advancing the development of radiopharmaceuticals, underpinned by comprehensive expertise in radiobiology, radiochemistry, radiopharmacy, and dosimetry. This multidisciplinary approach fosters an advanced research platform that accelerates the progression of innovative preclinical-stage nuclear medicine solutions.

With a dedicated team of over 100 professionals, NMA focuses on advancing the application of nuclear medical applications in the treatment of diseases, particularly cancer through the development of new radiopharmaceuticals.

Research areas and technological advancements

SCK CEN's research encompasses several critical areas in the development of radiopharmaceuticals and their application in targeted therapies:

• Development of carrier molecules for radioligand therapy with various potential therapeutic applications.
• Separation chemistry plays a central role in the production of high-purity radioisotopes for medical use, along with the recycling of raw materials. This expertise ensures that isotopes meet the stringent purity requirements necessary for medical applications.
• Decades of research into the radiation effects on the human body are now being leveraged to optimize radioligand therapies.

NMA has established a strong foundation in preclinical research, with a focus on optimizing the development pipeline from laboratory experiments to clinical studies. The integration of radiobiological principles and dosimetry ensures that radiopharmaceuticals are not only effective but also safe when applied in clinical settings.

Targeted cancer therapies: Radioligands and high-affinity ligands

A core focus of SCK CEN NMA's work is the development of radioligands—molecules designed to bind selectively to cancer cells and deliver targeted radiation to destroy tumors while minimizing damage to surrounding healthy tissue. The NMA institute's research includes:

• The design and synthesis of high-affinity ligands using peptide or chemical-based platforms that specifically target molecular markers on cancer cells.
• The formulation and validation of radioligands, where radiochemical binding of the ligand, chelator, and radioisotope is carefully tested to ensure precise delivery and prevent premature release of the radioisotope.
• In vitro studies assessing radiopharmaceutical uptake, cell viability, stress responses, and radiotoxicity in non-target areas, as well as radioligand behavior in living organisms to measure absorption, distribution, metabolism, and excretion.

Additionally, rigorous dosimetric analysis is performed to evaluate the radiation doses delivered to various organs and tissues, ensuring that these doses are within safe and effective limits. The overall aim is to translate preclinical data into clinical practice, optimizing radioligand therapies for human patients.

Hot Animal Facility (HAF)

The Hot Animal Facility (HAF) supports the development of radiopharmaceuticals with advanced preclinical studies. Comprising nine specialized laboratories, HAF conducts both in vitro and in vivo testing, ensuring safety and efficacy before clinical trials.

In in vitro tests, we assess radiopharmaceutical uptake, cell viability, and stress responses. For in vivo studies, we map radioisotope distribution in animal models, ensuring radiotoxicity control in non-target areas.

We also evaluate efficacy, dose-response, and survival curves, comparing treatments like radioligand therapy versus standard cancer treatments. This integrated approach helps optimize personalized therapies and advance radioligand therapies toward clinical application.

Translating preclinical research to clinical applications

The research at NMA is structured to provide a seamless transition from preclinical models to clinical applications. Key components include:

• Optimizing dosing protocols based on preclinical findings.
• Validating preclinical models to ensure they accurately represent human biology.
• Ensuring patient safety by conducting thorough radiobiology and dosimetry studies to guarantee the correct radiation dose is delivered to targeted cells while minimizing risks to healthy tissues.

This robust preclinical framework is designed to facilitate the subsequent transition to clinical studies, ensuring that treatments are safe, effective, and reproducible in human patients.

Centralized Radiochemical Facility (CRF)

A significant development in SCK CEN NMA’s infrastructure is the Centralized Radiochemical Facility (CRF), currently under construction, which will be instrumental in the GMP production of radiopharmaceuticals. Scheduled to come online in 2027, the CRF will initially focus on the production of n.c.a. lutetium-177, a critical isotope for radioligand therapies, while also being capable of processing next-generation isotopes.

The CRF will utilize advanced radiochemical separation techniques to produce isotopes that meet the stringent standards of the European Pharmacopoeia,ensuring the highest levels of chemical and radionuclide purity. In the short term, the CRF will support treatments for 15,000 patients per year, with long-term plans to increase production to serve 100,000 patients annually. This facility will be central to ensuring a stable and reliable supply of isotopes for clinical applications, particularly in radioligand therapy.

Collaborative efforts for a robust supply chain

The CRF’s production capabilities are further strengthened by a public-public partnership with the National Institute for Radio Elements (IRE), a Belgian institute with extensive experience in the distribution of medical radioisotopes. Through this collaboration, SCK CEN and IRE aim to establish a reliable and sustainable global supply chain for medical radioisotopes, ensuring that the isotopes produced at CRF can meet the growing global demand for nuclear medicine.

Another key partnership includes the development of terbium 161-based radiopharmaceuticals. In this context, a partnership with Terthera plays a crucial role by ensuring a robust and adaptable production infrastructure to support the next generation of radioligand therapies, further advancing nuclear medicine.

BR2 research reactor: A key component in radiopharmaceutical production

At the core of SCK CEN’s radiopharmaceutical production is the BR2 research reactor, a state-of-the-art facility that is pivotal in the production of essential medical isotopes, including molybdenum-99 and lutetium-177. Operating 203 days per year since 2019, BR2 ensures a continuous, reliable supply of isotopes to meet the needs of the medical community. On average, the reactor supports the diagnosis and treatment of over 11 million patients annually, playing a critical role in the global radiopharmaceutical supply chain.

The BR2 reactor is capable of producing 10 to 15 different radioisotopes per cycle, with a focus on molybdenum-99 and lutetium-177, both of which are crucial for diagnostic imaging and targeted cancer therapies.

Conclusion: Shaping the future of nuclear medicine

SCK CEN remains committed to advancing nuclear medical applications through continuous research, development, and the production of high-quality radiopharmaceuticals. With its integrated approach, state-of-the-art facilities, and deep expertise in the field, SCK CEN is poised to remain a global leader in radioligand therapies, ensuring the delivery of life-saving treatments to cancer patients worldwide.

Through its dedication to innovation and collaboration, SCK CEN is helping shape the future of nuclear medicine, offering hope to millions of patients in need of precision therapies.