Radiolabelled Peptide Synthesis with Tritium and Carbon-14
Poster Authors:
1 Pharmaron UK Ltd, Cardiff, UK
Radiolabelled peptide synthesis builds a radioactive label into a peptide during its assembly, so the finished molecule can be tracked through metabolism and distribution studies. Pharmaron labels peptides with tritium or carbon-14 and has completed more than 50 labelled peptide syntheses.
Pharmaron UK presented this work at a DMPK meeting in Oxford, UK in June 2026. The poster covers how the isotope and labelling position are chosen and the synthetic routes behind each. Complete the form to download it.
What is radiolabelled peptide synthesis?
Radiolabelling lets the absorption, distribution, metabolism and excretion (ADME) characteristics of a candidate drug be studied, which is a requirement for bringing a molecule to market. For peptides, a label also supports ligand binding, protein binding and receptor occupancy work. Building the label in during synthesis differs from tagging a finished molecule, and it gives control over exactly where the label sits.
Tritium or carbon-14: how is the isotope chosen?
Tritium gives high specific activity material, which suits binding studies, ADME work and low-dose administration. It is usually reached through short syntheses from precursor peptides, though standard on-resin synthesis can also be used. Carbon-14 gives moderate specific activity suited to ADME and clinical studies, prepared on resin. The choice follows what the study needs to measure.
Capabilities
How is the labelling position chosen?
Position is influenced by the metabolism of the peptide, where that is known, and by ease of synthesis. A label placed where metabolism cleaves it stops reporting on the parent molecule, so the two are weighed together. Non-labelled precursors or partially completed peptides on resin are needed as starting materials.
What about modified and longer peptides?
Longer peptides move beyond what precursor labelling reaches, so Pharmaron uses RadioTag, a tritiated reagent that radio-propionylates amino groups at the terminus or on lysine side chains. For modified peptides, Pharmaron has labelled conjugated lipids and PEGs both within the peptide and in the attached groups, including several semaglutide analogues. Carbon-14 labelled amino acids are produced with high enantiomeric purity.
Why does the isotope choice matter for imaging?
Tritium and carbon-14 can give higher resolution in quantitative whole body autoradiography (QWBA) images than iodine-125, and neither changes the structure of the parent peptide. Iodination adds atoms to the molecule, so what is imaged is no longer quite the peptide under study. The poster includes a rat QWBA comparison.
Key takeaways
- Tritium suits binding studies, ADME and low-dose work; carbon-14 suits ADME and clinical studies.
- Labelling position is chosen from the metabolism of the peptide and the ease of synthesis.
- RadioTag extends labelling to peptides longer than precursor routes reach.
- Pharmaron has completed more than 50 labelled peptide syntheses, including modified peptides with lipids and PEGs.
What is in the poster
The poster sets out the tritium precursor-labelling strategies with their specific activities, the carbon-14 routes and enantiomeric purities, the practical considerations for each residue type, typical synthesis scales and durations plus the rat QWBA image comparison. Complete the form to download it.
Frequently asked questions
What is radiolabelled peptide synthesis?
It is the preparation of a peptide with a radioactive label built in during assembly, so the molecule can be tracked in metabolism and distribution studies.
Should a peptide be labelled with tritium or carbon-14?
Tritium gives high specific activity for binding studies, ADME and low-dose administration. Carbon-14 gives moderate specific activity suited to ADME and clinical studies.
How is the labelling position decided?
From the metabolism of the peptide where it is known, together with ease of synthesis, so that the label stays on the part of the molecule being followed.
Can long or modified peptides be radiolabelled?
Yes. RadioTag covers peptides beyond the reach of precursor labelling, and Pharmaron has labelled peptides modified with conjugated lipids and PEGs.
