Progressing a novel radiopharmaceutical towards clinical development requires a clear understanding of its radiochemical properties, biological behaviour, tissue distribution and potential safety risks. For developers, generating this evidence can be challenging. Radiolabelling performance, target engagement, imaging, biodistribution and dosimetry are closely interconnected, and decisions made at one stage can significantly influence the next. At Medicines Discovery Catapult (MDC), our integrated radiopharmaceutical translational research capabilities bring together radiochemistry, in vitro biology, preclinical imaging, biodistribution and dosimetry to support informed candidate selection and preclinical development that supports an investigational new drug (IND) or clinical trial application (CTA) submission. By designing studies around the scientific and regulatory questions specific to each programme, we help developers identify risks earlier, strengthen their preclinical evidence and make more confident decisions about progression towards the clinic.

MDC is a life sciences service. We exist to help entrepreneurial scientists make their next move count. Providing access to world-class expertise, advanced facilities, and collaborative partnerships. MDC is continually transforming and de-risking the drug discovery process. Radiopharmaceuticals offer real promise where patients have limited treatment options, particularly in oncology. However, advancing these targeted therapies requires high-quality translational data.

In this article, we outline our framework for building an IND-enabling preclinical package. By integrating cellular assays and translational imaging, we help you to generate evidence that supports regulatory discussions and accelerates your path to the clinic.

Meeting strict radiopharmaceutical regulatory expectations

Regulators expect strong evidence before a radioactive compound enters human trials. A complete IND submission, or CTA in the UK and Europe, covers far more than preclinical studies, including toxicology, manufacturing and clinical information. For a radiopharmaceutical, this evidence should show how the drug behaves from administration to clearance, whether it reaches its intended target and how stable it is in the body. MDC generates integrated preclinical evidence to support IND-enabling development and the regulatory activities required for progression into clinical trials.

Gaps in the data at this stage can mean incredibly costly delays, lengthy clinical holds, or requests for further work. Our team at MDC understands these regulatory hurdles well, and our approach follows US Food and Drug Administration (FDA), Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA) guidance for radiopharmaceuticals. We continually design preclinical programmes around the questions regulators are likely to ask.

Our step-by-step approach to building an IND-enabling package includes several critical stages:

• Developing reliable radiolabelling and stable formulation strategies.
• Running targeted in vitro assays to measure binding and internalisation.
• Conducting translational in vivo imaging to monitor real-time distribution.
• Performing biodistribution and dosimetry studies to estimate absorbed radiation doses.
• Testing preclinical efficacy, including tumour growth inhibition and survival benefit.

Starting with robust radiolabelling

Every successful radiopharmaceutical programme begins with sound radiochemistry. Before any biological testing can start, you need a reliable radiolabelling and formulation strategy. Our radiolabelling services cover small molecules, peptides, proteins and other biologics carrying alpha, beta or gamma-emitting radiometals. We optimise how the isotope attaches, using chelators such as DOTA, Macropa and deferoxamine (DFO), and we check that the chelator and linker hold it securely.

If a radiopharmaceutical releases its payload too early in the bloodstream, it can cause off-target toxicity and weaken tumour uptake. We measure radiochemical yield and purity with high-performance liquid chromatography (HPLC), instant thin-layer chromatography (ITLC) and gamma spectrometry, and we have reached radiochemical purity above 97 per cent for complex alpha and beta-emitting conjugates. Early optimisation of this kind helps to de-risk the pipeline.

In vitro radiopharmaceutical therapy screening

Once a stable radiolabelled compound is obtained, we move to in vitro radiopharmaceutical therapy screening. We run binding assays to measure affinity and show how strongly the drug binds its target receptor.

We also assess cellular internalisation and retention to understand how radiopharmaceuticals interact with target cells. These characteristics can influence tumour uptake, residence time and therapeutic activity, depending on the radionuclide and targeting mechanism. MDC scientists design bespoke cellular assays to quantify how much of your drug enters the cell and how long it stays there. This early data helps to prioritise candidates and identify those less likely to perform in a living organism.

Advancing to translational imaging

When cellular data supports target engagement and stability, the next step is in vivo biology. This is where we gather translational data that supports IND-enabling development.

Our imaging facility offers positron emission tomography (PET) and single-photon emission computed tomography (SPECT), which we combine with computed tomography (CT). Together, these deliver quantitative PET/CT and SPECT/CT imaging. They provide non-invasive measurements of where the drug travels. By imaging the same animals over time, we monitor tissue uptake across hours or days, matched to the half-life of your isotope (for example, lutetium-177 has a half-life of about 6.7 days). This approach helps assess target engagement and off-target accumulation in living systems, using the same imaging modalities that clinical teams use in patients.

We can also pair diagnostic and therapeutic isotopes, such as zirconium-89 and lutetium-177, for preclinical theranostic validation that can inform patient selection strategies.

Mapping biodistribution and dosimetry

Regulators expect a clear understanding of radiation safety before a trial begins. To support this understanding, we deliver integrated biodistribution and dosimetry services.

Biodistribution studies involve measuring the radioactivity in specific organs and tissues at various time points. We use ex vivo analysis, such as gamma counting and autoradiography, to validate our non-invasive imaging data. This gives a detailed view of tissue uptake, showing whether the drug concentrates in the tumour or accumulates in healthy organs.

By integrating biodistribution measurements with dosimetry modelling, we estimate absorbed doses to tumours and normal tissues. These data can inform candidate selection, identify potential dose-limiting organs and contribute to human dose projections and first-in-human study planning. Predicted human doses depend on assumptions about biological distribution and species differences, so they complement toxicology data rather than replace it.

Assessing preclinical therapeutic efficacy

The final stage is assessing whether the drug shows therapeutic activity in preclinical models. We conduct tailored preclinical efficacy studies to measure tumour growth inhibition or survival benefit. By combining efficacy data with our imaging and dosimetry findings, we build a coherent body of evidence.

The aim is to show whether the drug reaches its target, delivers a defined radiation dose and causes a measurable therapeutic effect in preclinical models. These studies do not replace toxicology or clinical trials, but a multi-layered approach gives regulators a clearer evidence base for assessing your move into the clinic.

Partnering to reach patients faster

The technical and regulatory challenges are significant, but they are not insurmountable with the right expertise. MDC is deeply committed to supporting programmes that bring transformative therapies to patients faster.

We bring radiochemistry, in vitro biology, imaging and dosimetry together at one secure UK site, with access to isotopes such as lead-212 through partners including the UK National Nuclear Laboratory. Our team works alongside yours, shares data openly and challenges the science where it helps your programme. With everything under one roof, we assemble an IND-enabling preclinical package to support your regulatory submission.

Together, we can shorten the road to clinical trials and move new treatments towards the patients who need them.

Speak to us today

If you are ready to build a preclinical package for your radiopharmaceutical, our team is here to help.

Complete the contact form on our preclinical radiopharmaceutical services page to discuss your IND-enabling studies.

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