Why radiopharmaceuticals are becoming central to precision oncology

Radiopharmaceuticals are rapidly moving from a specialist niche to a central position in precision oncology, offering a highly targeted way to deliver cytotoxic radiation to cancer lesions while limiting systemic exposure. As oncology development shifts away from broad, non-selective cytotoxic, these agents are gaining clinical and commercial momentum.

At the same time, radiopharmaceuticals are opening a new strategic opportunity for biotech and pharma companies under pressure to differentiate pipelines: repurposing existing oncology molecules as carriers for radionuclides. However, translating this opportunity into viable clinical candidates is complex, requiring the integration of oncology, biology, radiochemistry, operational planning and evolving regulatory expectations.

What makes radiopharmaceuticals fundamentally different

Radiopharmaceuticals represent a distinct class of oncology therapeutics, combining biologically active molecules with radionuclides to enable targeted delivery of radiation to cancer cells. Unlike conventional oncology drugs, where therapeutic efficacy depends on the pharmacological activity of the active pharmaceutical ingredient (API), radiopharmaceuticals rely on the radionuclide to deliver the therapeutic effect.

The role of the targeting molecule, whether a small molecule, peptide, antibody or antibody-drug conjugate (ADC), is primarily to guide the radionuclide selectively to tumour tissue. Then, the emitted radiation induces cytotoxic damage within the tumour while limiting exposure to surrounding healthy tissues. As the radionuclide provides the primary therapeutic action, radiopharmaceuticals require 100- to 1,000-fold lower quantities of the targeting molecule compared with established systemic therapies.

This reduction in required dose has important implications for oncology drug development, as the targeting molecule no longer needs to sustain a pharmacological effect and dose-limiting toxicities that halted conventional drug programmes may not be observed. As a result, molecules that failed to progress in clinical phases due to toxicity or narrow therapeutic impact may still be suitable as tumour-targeting carriers for radionuclide delivery.

Repurposing oncology assets for radiopharmaceutical development

When repurposed as carriers for therapeutic radionuclides, APIs that retain sufficient tumour affinity, despite having failed, can be redeployed to deliver cytotoxic radiation to cancer cells, without relying on sustained systemic pharmacological activity. This enables developers to revisit assets that were previously shelved or deprioritised, while leveraging existing knowledge of tumour targeting and biology.

This repurposing strategy is not limited to failed compounds alone. Biologics, peptides, antibodies and ADCs that have already demonstrated robust tumour targeting can also serve as effective radiopharmaceutical platforms. For developers, this approach offers a strategic opportunity to extend the value of existing portfolios, accelerate development timelines by leveraging prior knowledge and create new intellectual property and lifecycle management options within an increasingly competitive oncology landscape.

However, radiopharmaceutical development is not a straightforward extension of conventional oncology drug development.

Key challenges in radiopharmaceutical development

Repurposing existing assets into radiopharmaceutical introduces a distinct set of scientific, operational and regulatory challenges that must be addressed early if programmes are to progress efficiently.

1.   Integrating oncology biology and radiochemistry

Radiopharmaceutical development requires the integration of two highly specialised disciplines that are rarely combined within conventional oncology programmes. Successful translation depends on understanding tumour biology and targeting, alongside the principles of radiochemistry and bioconjugation.

From a biological perspective, developers must ensure that the targeting molecule selectively localises tumour tissue and demonstrates sufficient uptake and retention to deliver a therapeutic radiation dose. Key considerations include target expression, binding affinity, internalisation and pharmacokinetics and pharmacodynamics (PK/PD). However, bioconjugation and radiolabelling can alter molecular behaviour. Suboptimal conjugation strategies may compromise targeting efficiency or lead to premature radionuclide release, resulting in unfavourable biodistribution and off-target radiation exposure. Radionuclide and chelator selection must therefore balance biological performance with radiochemical features and clinical feasibility.

2. Operational constraints driven by radionuclide physics

Operational complexity is a defining feature of radiopharmaceutical development. Working with radioactive materials requires dedicated facilities, specialised equipment and strict safety procedures to manage radiation exposure and waste. These activities also rely on experienced personnel, including specialists in radiochemistry and radiopharmacology, to ensure that studies are conducted safely, reproducibly and in compliance with regulatory standards.

Logistics adds a further layer of complexity. Many radionuclides decay rapidly, placing tight constraints on the timing of radiolabelling, administration and downstream analysis. Development activities must therefore be carefully synchronised, with radionuclide availability aligned precisely with chemistry workflows and the readiness of preclinical models. Even small delays can render a radionuclide unusable, leading to lost material, repeated studies and extended timelines.

Without early consideration of supply robustness, programmes can stall during translation from preclinical research to clinical development. Radionuclide selection should therefore be guided by theoretical performance and realistic availability across preclinical and clinical phases, with operational feasibility assessed from the outset.

3. Rising regulatory expectations

Agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have become increasingly familiar with radiopharmaceuticals, but this has been accompanied by more rigorous and clearly defined expectations.

Regulatory submissions require robust radiochemistry validation, including detailed characterisation of the quality, stability and purity of conjugated compounds. In addition, comprehensive biodistribution and dosimetry data are needed to demonstrate targeted tumour uptake and to quantify radiation exposure to healthy tissues. Efficacy and toxicity profiles must also be established through appropriately designed preclinical studies, including non-good laboratory practice (nGLP) and GLP investigations where required. Importantly, repurposing an existing oncology API does not remove the need for a radiopharma-specific regulatory data package.

Engaging regulatory strategy early and designing studies with clinical translation in mind can reduce the risk of delays at IND-enabling stages and support smoother progression toward the clinic.

De-risking the journey through an integrated development approach

Radiopharmaceutical development places unique demands on programme design, requiring scientific, operational and regulatory considerations to be addressed in parallel rather than sequentially. Success is most likely when development is designed as an integrated system from the outset, rather than a series of disconnected activities. Scientific feasibility, operational constraints and regulatory requirements must be considered to avoid late-stage redesign, delays or attrition. An effective radiopharmaceutical development approach therefore brings together multiple capabilities within a single, coordinated framework.

In practice, this should include:

• Bioconjugation and radiochemistry development
  Early optimisation of chelators, radionuclide selection and radiolabelling strategies is essential to ensure stability and reproducibility without compromising tumour targeting. Radiochemistry decisions made at this stage have direct implications for downstream biology, operations and regulatory readiness.
• PK/PD assessment and biodistribution
  Evaluating pharmacokinetics, pharmacodynamics and in vivo biodistribution helps establish whether sufficient tumour uptake and retention can be achieved while limiting exposure to healthy tissues. These data are critical for both candidate selection and translational planning.
• Relevant preclinical oncology models
  Access to appropriate in vivo and ex vivo models enable early proof-of-concept testing and iterative optimisation, supporting faster and more informed go/no-go decisions.
• Imaging, dosimetry and toxicity evaluation
  Integrated imaging and dosimetry provide quantitative insight into radiation delivery and organ exposure, supporting both efficacy assessment and the generation of regulatory-relevant data packages.

CROs that can coordinate these elements within a single development strategy help developers identify risk earlier, align timelines more realistically and generate coherent, clinic-ready data packages. In radiopharmaceutical development, this integrated partnership model can significantly de-risk radiopharmaceutical programmes and accelerate their progression toward clinical translation.

Radiopharmaceuticals as a platform, not a trend

Radiopharmaceuticals are increasingly being viewed not as a single therapeutic modality, but as a flexible development platform with broad applicability across oncology. The long-term impact of radiopharmaceuticals will be defined less by individual technologies and more by how programmes are designed and executed. The repurposing of existing oncology assets illustrates this clearly. By redefining the role of known molecules as tumour-targeting carriers, developers can move away from one-off breakthroughs and toward repeatable, scalable approaches that reduce risk while accelerating progress.

As competition intensifies and development timelines come under increasing scrutiny, radiopharmaceutical success will favour organisations that take a strategic and realistic approach. Integrating scientific, operational and regulatory considerations early and collaborating across disciplines and with experienced partners will be essential. Treating radiopharmaceuticals as a long-term development platform rather than a passing trend offers the greatest opportunity to translate scientific progress into tangible clinical benefit, improving the outcomes and quality of life for patients with cancer worldwide.