Absorption, distribution, metabolism, and excretion (ADME) studies are typically performed through Phase 1 and 2 of clinical research to meet the regulatory requirements for understanding and characterising how a drug and its key metabolites move through the body.
In this blog Alan Jeuken, Director, Drug Development Consultant, and Edwige Picazo, Drug Development Associate, Scientific Consulting, explore how our isotope labelling expertise integrates seamlessly with Arcinova’s broader CMC capabilities to deliver bespoke 14C drug substance and drug product programmes tailored to wider study needs. They also discuss how combining isotopic labelling with human ADME studies delivered by Quotient Sciences can streamline drug development and significantly accelerate time-to-market for new therapies.
1. Why do ADME studies often involve radiolabelling?
ADME studies often utilise a radiolabelled form of the investigational drug, enabling easier detection and quantitative measurement of the parent compound and metabolites in clinical samples. This approach supports the generation of high-quality data about your drug metabolism, as well as routes and rates of elimination for regulatory submissions.
Recently, there has also been a growing need to determine the absolute bioavailability of poorly soluble drugs. To support formulation decision making for oral products, many drug developers are now incorporating a radiolabelled IV microtracer (IVMT) arm into the traditional clinical ADME study design.
Carbon-14 (14C) is the isotope of choice for these human ADME/IVMT studies because of the ubiquity of carbon in small molecules and easier administration in human volunteers as a low energy beta-emitter with a long half-life (> 5000 years).
2. How do scientists decide where to place the radiolabel in a molecule?
The first consideration during the development of radiolabelled materials is around labelling strategy; optimal positioning of the 14C label in a metabolically stable part of the molecule is crucial to ensure all key metabolites are identifiable. This labelling strategy significantly influences the timelines and study budget, which depends on the availability of the radiolabelled starting materials, the number of synthetic stages, the complexity of the chemistry, and the ease of isolation.
3. What challenges influence the design of synthetic routes for 14C radiolabelling?
Unlike the broad options in medicinal chemistry or process chemistry routes, the limited availability of commercially available 14C-labelled starting materials means syntheses are restricted to start from a small pool of radiolabelled building blocks such as 14CO2 and K14CN. Consequently, designing the synthetic route often involves a trade-off between introducing the radiolabel at a late stage—typically on a more exposed part of the molecule—or incorporating it into the core structure. While the former approach can reduce costs and shorten timelines, the latter offers greater metabolic stability, often resulting in more reliable and complete metabolite identification and quantification data.
4. What radiolabelling capabilities does Arcinova offer to support 14C ADME studies?
- Isotopic labelling services to synthesise 14C-labelled drug substance
- Formulation development to produce fit‑for‑purpose oral or parenteral drug products
- Integrated services to support both non clinical and clinical 14C ADME studies
At Arcinova, we offer isotopic labelling services to support both non clinical and clinical 14C ADME studies. Our expert synthetic chemists bring over 40 years of radiolabelling experience and have delivered more than 500 small molecule radiosynthesis programmes. They are fully trained and authorised in the safe handling of 14C labelled gases and volatiles—including 14CO₂, 14CO, and 14COCl₂—as well as high potency and high hazard 14C materials such as cytotoxics and controlled substances, ensuring safe, reliable and on time study delivery.
Following the synthesis of the isotopically labelled drug substance, our formulation team develops fit-for-purpose oral or parenteral formulations tailored to your programme needs. With the growing popularity of absolute bioavailability investigations—where an IVMT arm is combined with a traditional ADME study—the demand for specialised radiolabelled sterile manufacturing has increased rapidly. With over 30 years of parenteral development expertise, we deliver specialised IV, SC and IM formulations that ensure robust, EU GMP Annex-1 compliant radiolabelled sterile drug products for 14C ADME and Absolute Bioavailability studies.
5. What does Arcinova do behind the scenes to make planning and delivering radiolabelled materials simpler and more efficient?
We offer up-front expert consultancy to design isotopically labelled synthetic strategies and fit-for-purpose drug product formats. We continually review external and internal radiolabelling methodologies and advances in the field of 14C synthesis combined with fit-for-purpose formulation development to ensure that we propose and deliver innovative, efficient radiolabelled CMC programmes aligned with your drug development timelines.
When onboarding your programme, each project receives dedicated attention from a technical chemist lead, analytical lead, regulatory lead and project manager who collaborate regularly internally and with you for seamless programme delivery. Every molecule radiosynthesis and formulation is unique and by combining our radiolabelling expertise with your knowledge of your drug development program we construct the best path forward in a collaborative effort.
We provide our customers with a forward thinking and solution-focused approach throughout all phases of 14C drug development, from early synthesis development through to regulatory submission.
For example, synthesising a radiolabelled preclinical intermediate that can be used for both non-clinical and clinical batches; eliminating the need for re-synthesis saves time and reducing costs associated with providing labelled materials for both animal and human ADME studies.
6. What is the Synthesis-to-Clinic® approach, and how does it shorten the drug development process?
Integrating Arcinova’s radiolabelling services with Quotient Sciences’ clinical expertise, Synthesis to Clinic® builds on the company’s position as a world leader in 14C radiolabelled study conduct and serves as a core component of the Translational Pharmaceutics® platform, enabling us to accelerate timelines from initial radiosynthesis through to the delivery of both clinical study and metabolite characterisation reports. By integrating drug substance, drug product, and clinical activities within a single organisation, Translational Pharmaceutics® breaks down traditional industry silos to deliver measurable advantages for drug developers.