How are radioligand therapies transforming cancer care?

21 Jan 2026 9min read

A cure for cancer is often held up as a metaphor for a miracle, or at least a goal that is considered potentially out of reach. “The big C” remains one of our most formidable health challenges, with roughly 1 in 5 people developing cancer in their lifetime and approximately 1 in 9 men and 1 in 12 women dying from the illness. The burden is growing, with the number of new cancer cases expected to increase by 77% from 2022 to 2050.

Despite huge advances in diagnosis and treatment including surgery, chemotherapy, radiotherapy, brachytherapy, targeted drugs and immunotherapy, many cancers remain resistant to treatment, recur after therapy or spread to other parts of the body. A field of research and innovation seeking to deliver improved outcomes is radioligand therapy (RLT). The treatment combines the specificity of molecular targeting with the destructive power of radiation to offer a more precise, effective and less toxic approach.

RLT, sometimes referred to as targeted radionuclide therapy (TRT), represents a major shift in oncology and nuclear medicine. Unlike external beam radiation, which irradiates broad areas or chemotherapy, which affects rapidly dividing cells indiscriminately, RLT delivers radiation directly to tumour cells, sparing most surrounding healthy tissues.

This article explores this complex, ground-breaking and exciting therapy area, including some of the key concepts, applications, benefits and challenges.

An overview of radioligand therapy

At a basic level, RLT involves administering a compound that combines two critical components:

A radioactive isotope (radionuclide) – emits ionizing radiation, killing cells through DNA damage and oxidative stress
A targeting ligand – is a molecule that binds specifically to a receptor or antigen present on tumour cells.

By fusing these components using a ‘linker’, the therapy facilitates the delivery of lethal radiation directly to pathological tissue. The radioligand is introduced, often via intravenous infusion, and travels through the bloodstream until it binds onto receptors on the targeted tumour cells. The ligands then transport the radionuclide inside the cell where the radiation is delivered, resulting in cumulative damage to the DNA which kills the cancerous cells. Cancer cells are particularly sensitive to radiation-induced DNA damage.

There are different types of radionuclide and targeting ligand.

Radionuclides - alpha and beta particles

The first application of radioligand therapy was developed in the 1940s whereby radioactive iodine (I)-131 was used to treat some types of thyroid cancer. This method was made possible because the thyroid absorbs all of the iodine that enters the body, creating a natural, biological ligand.

Advances in molecular biology, imaging and radiochemistry led to the development of other radionuclides and ligands.

Zevalin, a Yttrium-90 (Y-90) and Indium-111 (In-111) based radioimmunotherapy treatment, and Bexxar, an I-131 based radioligand, were approved in the 2000s. More recently the manufacture of Lutetium-177 (Lu-177) has become more widespread leading to the development of Lu-177 based radioligands such as Lutathera®, approved in Europe in 2017 for the treatment of neuroendocrine tumours, and Pluvicto®, approved in Europe and USA in 2022 to treat prostate cancer. Y-90, Lu-177 and I-131 each emit radioactive beta particles.

However, the greatest recent developments have been in alpha radioligand therapeutics, based on alpha particle emitters. None have yet been approved yet other alpha targeted therapies, such as Xofigo®, are commercially available. Actinium-225 (Ac-225) and Lead-212 (Pb-212) are two examples currently in clinical trial phase, the former for the treatment of prostate cancer and the latter for the treatment of solid tumours. Their potential is reflected in commercial terms by predictions of growth in global market value for alpha emitters from $670M in 2020 to $5.2B by 2027.

To compare beta and alpha particles at the highest level:

Beta particles can travel further, including through tissue, than alpha particles which move only a few cell diameters and can be blocked by membranes such as a piece of paper. This means that alpha particles are less likely to damage
Alpha particles have much more ‘energy’ and cause dense, irreparable damage to DNA. Beta particles are less powerful and cause damage more cumulatively.

Ligands - what are the different types

Ligands are comprised of molecules such as folic acid, carbohydrates, peptides, aptamers or antibodies. They exhibit structural diversity and have different strengths and weaknesses, but all specifically bind to receptors that are overexpressed on tumour cells and minimally expressed in normal tissues. Ligand types include:

Small Molecules: chemical simplicity and low cost but with limited aiming

Carbohydrates: naturally occurring and biocompatible but with variable targeting

Peptides: highly customisable with good biodegradability but high preparation costs and short half-life

Aptamers: high specificity and easy to synthesise but poor stability in the body

Antibodies: high sensitivity and high immunogenicity but high preparation costs.

Of the 13 therapeutic radiopharmaceuticals approved worldwide as of now, six are radioligands. Of these, two are small molecules, Pluvicto® and Azedra. One is a peptide, Lutathera®, and the remaining three are monoclonal antibodies, Zevalin, Licartin and Bexxar.

The remaining seven approved therapeutic radiopharmaceuticals are non-ligand-based and target tumours either by physiologic or physical mechanisms. Examples of physiologic targeting include Xofigo® (Radium-223 (Ra-223) dichloride), which behaves like calcium and selectively localises to areas of increased bone turnover, such as bone metastases. Physical targeting is exemplified by SIR-Spheres, Y-90 resin microspheres, which are injected intra-arterially into the hepatic arteries feeding liver tumours, where they lodge mechanically and deliver localised radiation.

Advantages, risks and challenges of RLT

The key advantage of RLT is the precision targeting that is affords, minimising collateral damage to surrounding healthy tissue as compared to chemotherapy or external radiation. It is generally well tolerated with manageable side effects. In addition, the systemic nature of the treatment enables access to cancerous lesions throughout the body and it can be effective in resistant disease, both of which offer hope to patients with limited treatment options.

An additional application of the ligand technique, used in conjunction with RLT, is to combine them with diagnostic radionuclides, which allows both identification of eligible patient and prediction of therapy effectiveness. One example is Illucix, a Gallium-88 (Ga-88) bound to PSMA, which can be imaged with positron emission tomography (PET). This integration of radionuclide therapy with diagnostic nuclear medicine imaging is known as ‘theranostics’.

RLT offers exciting opportunities in the field of oncology, but also brings numerous challenges.

The first is that it demands non‑standard approaches to supply chain and administration. Many radionuclides have very short half-lives, meaning that they need to be delivered within days of generation from complex manufacturing systems. This requires the highly specialised generators to be located relatively close to the point of use. Both Zevalin and Bexxar were withdrawn from the market not because of safety of efficacy concerns but due to the challenges of logistics and commercialisation.

Secondly, the safety of those handling the RLT from manufacture to patient delivery, is paramount. Packaging, infusion systems and disposal routes are all must be bespoke to the radioisotope concentrations being handled, which can increase the cost and availability of these treatments, restricting access particularly in low and middle-income countries.

In terms of the treatment itself, variability in tumour characteristics can impact effectiveness of treatment. This includes the levels at which cells express target receptors, and the difficulty in determining optimal dosage.

Future developments in radioligand therapy

The field of radioligand therapy is rapidly evolving, across numerous promising areas including the list below.

Combination therapies – RLT is integrated with other elements, such as PARP inhibitors which prevent the tumour cells repairing the damage caused.
Expanded targets – research identifies new biomarkers, for example HER2 which is linked to breast cancer and EGFR linked to glioblastoma, a cancer of the brain.
Personalised dosimetry – advanced imaging and computational modelling will allow individualised treatment planning, balancing efficacy with safety.
Manufacturing technologies – new technologies are being developed which seek to increase production volumes and/or allow more localised generation of the radionuclides.
Nanotechnology-based delivery – nanoparticles such as gold particles may enable multi-radionuclide payloads to be accurately delivered for improved performance and reduced off-target toxicity.

Antibody-drug conjugates (ADCs) have similarities to RLTs, but instead consist of monoclonal antibodies that target specific surface antigens present on tumour cells (rather than ligand), that are conjugated to cytotoxic payloads (rather than radionuclides) which cause the damage.

Conclusion

Many of the leading global pharmaceutical companies are committed to improving treatments in the oncology sector, including Novartis who own both Lutathera® and Pluvicto®, and radioligand therapy will be an important part of this.

RLT is a highly technical field, characterised by complex science and with future successes dependent on significant ongoing research and investment. Meeting and resolving the challenges faced, including how to make treatment accessible and affordable, will be difficult, but the opportunities identified are hugely encouraging. Many people have already had their lives changed, and saved, by these treatments.

There are many changes needed to reduce the impact of cancer on global healthcare, including continuing to address, where possible, the root causes. Radioligand therapy can be a major part of improving outcomes.