Radionuclides: a sourcing challenge

Overcoming radionuclides supply challenges with innovative solutions by Oncodesign Services

The concept of using radioactivity to treat cancers is not new. A good example is iodine-131, a mainstay of thyroid cancer therapy. Recently, we observed a surge in interest in targeted radiotherapeutics (TRT), where molecules with a biological function are used to deliver radionuclides selectively to cancer cells.

Following on from the approval of Novartis’s Lutathera, which treats neuroendocrine tumours and uses lutetium-177, there has been an increasing number of potential radiopharmaceuticals in the early stages of development, using a variety of different radionuclides.

A new breed of radionuclides

This interest in TRT has led to a growing demand for the different radionuclides but also for new ones to address diverse approaches of internal radiotherapy such as beta vs alpha emitters. Getting hold of some of them is becoming an increasing challenge. And without ready access to the right radionuclides, neither preclinical translational research nor clinical trials of potential new radiopharmaceuticals can go ahead.

The range of radionuclides being investigated is expanding. The well-established ones, such as lutetium-177, are being joined by a multitude of alternatives. These include the theranostic pair of copper isotopes, copper-64 and copper-67, with the former used for PET imaging and the latter having therapeutic potential. Others of growing interest include alpha emitters such as actinium-225, astatine-211 and lead-212, as well as beta emitters such as terbium-161 as the potential counterpart for lutetium-177.

The Challenges in supply

Geopolitical considerations are a significant factor in the shortages, with Russia being one of the main sources for some of them. But as well as geopolitical issues, the absence of adequate production methods is a real problem.

Alternatives to lutetium are of particular interest right now because the supply of raw material is so skewed towards Russia. Once the production of one alternative such as terbium-161, will progress, it should compensate for the lutetium-177 shortage in the near future. Another particularly ‘hot’ radionuclide is actinium-225, which is showing promise in analogous drugs to those containing lutetium-177. Studies indicate that actinium as an alpha emitter, appears to have a more prominent therapeutic efficacy. This leads to an increase demand for its use in the preclinical and clinical set up. Yet the production technology of actinium-225 is at its infancy resulting in the production of limited amounts not able to cover current and future needs.

Bristol-Myers Squibb recently acquired RayzeBio, which has an actinium-225 analogue of Lutathera in development. This analogue has gone straight into Phase 3 trials for neuroendocrine tumours after interim results of a Phase 1b trial indicating it is more efficacious than Lutathera, including against metastatic disease. However, supply chain issues meant patient recruitment had to be paused for at least 6months before resuming actions recently following the secure of actinium-225 supply. If even a company in Phase 3 trials is struggling to source actinium-225, the inevitable result for the wider field of radiotherapeutics is that the shortage will be even more pronounced.

Some companies have pressed on with trials on molecules containing alternative isotopes regardless, and are attempting to establish supply chains directly with suppliers. But this causes further problems for those engaged in early exploratory preclinical work – with needs of limited amounts, suppliers will naturally prioritise those companies who are in the clinic, where larger amounts are required. This consequently squeezes out those still in the preclinical stage.

How to secure a radionuclide supply chain for your TRT preclinical programs?

As a potential radiotherapeutic moves closer to the clinic, the ability to source the radionuclide comes into sharp focus. Here at Oncodesign Services, we have put significant effort into building a supply chain for radionuclides covering also the respective logistic challenges to support our contract research services in the field of TRT. We have a long-standing experience and extensive expertise in radiochemistry and in developing radiopharmaceuticals.

Over the years we have built up a network of commercial enterprises and academic centres, in Europe and recently with a new partner in North America, who work with us to provide all the different radionuclides required for our customers’ research projects.

We have foreseen the exponential increase in demand for newly developed radionuclides hence, we have secured access to a wide range of different radionuclides. Our list of available radionuclides ranging from the more established ones such as lutetium-177, indium-111, iodine-125/131, zirconium-89, to those where the supply chain is still in its infancy. Importantly, the latter includes both actinium-225 and terbium-161, as well as the two copper isotopes (copper-64/67).

Oncodesign Services has established a strategic alliance, DRIVE-MRT (DRIVE-Molecular RadioTherapy), to provide support to your preclinical programs from bench to bedside for the development of radiopharmaceutical in a rapid and reliable way. Our DRIVE-MRT program is based on our established network of radionuclide suppliers, logistic chain and laboratories with extensive expertise, even in some cases with in-house productions. 

If you would like to know more about molecular radiotherapy (MRT)/TRT and how Oncodesign Services can support your projects, get in touch via the contact form below.

Or if you are interested to know more how to repurpose your cancer drug to MRT, read our article by Dr Efthychia Koumarianou!