Radiochemistry in Positron Emission Tomography

Radiochemistry underpins the production of radiotracers for PET, a non-invasive imaging modality that quantifies biochemical processes at the molecular level in vivo. Central to PET is the incorporation of short-lived positron-emitting radionuclides—most commonly fluorine-18 and carbon-11—into biomolecules that target specific physiological pathways. Advances in chemical synthesis have expanded the repertoire of synthons amenable to radiolabelling, enabling the construction of structurally diverse tracers for oncology, neurology and cardiovascular applications. Key innovations include transition metal–mediated radiofluorination to access electron-rich arenes, deaminative approaches to heteroaromatic scaffolds, and photoredox-driven methodologies that offer mild and selective transformations. The integration of statistical design of experiments and novel fluoride elution techniques has enhanced reaction reproducibility and automated production, facilitating clinical translation. Emerging strategies harness bioorthogonal conjugation for high-molecular-weight ligands and scalable processes that comply with good manufacturing practice. Together, these developments have not only broadened the chemical space of PET agents but have also improved accessibility, specific activity and throughput across research and diagnostic settings worldwide.

Research from Nature Portfolio

Recent studies have provided a comprehensive survey of chemical transformations utilised in PET tracer synthesis. One work delineates common radiochemistry pathways, from nucleophilic and electrophilic radiofluorination to metal-catalysed carbon-11 incorporation, and highlights scalable protocols that have entered clinical evaluation. It places particular emphasis on the application of biologicals as imaging probes and showcases translational case studies that bridge preclinical discovery with patient studies. Another investigation applies a design of experiments framework to copper-mediated 18F-fluorination of arylstannanes. By mapping factor interactions and employing multivariate screening, researchers achieved more than two-fold greater experimental efficiency, elucidated critical reaction parameters and refined conditions for automated radiosynthesiser platforms, exemplifying how systematic optimisation can accelerate the development of new PET tracers.

Radiochemistry in Positron Emission Tomography publication trend

The graph below shows the total number of articles in radiochemistry in positron emission tomography across all publications each year (not limited to Nature Index journals).

Technical terms

Radiotracer: A molecule labelled with a positron-emitting radionuclide for in vivo imaging of biochemical processes.

Synthon: A reactive molecular fragment or precursor used as the building block in radiolabelling syntheses.

Radiofluorination: The chemical incorporation of fluorine-18 into organic molecules, typically via nucleophilic or electrophilic pathways.

Photoredox catalysis: A light-driven catalytic process that enables redox transformations under mild conditions, often used to generate radioisotope-labelled intermediates.

Prosthetic group: A small, pre-labelled reactive moiety that is conjugated to biomolecules to facilitate radiolabelling without harsh conditions.

References

1. Radiochemistry for positron emission tomography. Nature Communications (2023).
2. Expedient Access to 18F‐Fluoroheteroarenes via Deaminative Radiofluorination of Aniline‐Derived Pyridinium Salts. Angewandte Chemie International Edition (2024).
3. One-Step Synthesis of [18F]Aromatic Electrophile Prosthetic Groups via Organic Photoredox Catalysis. ACS Central Science (2024).
4. Spirocyclic Iodonium Ylides for Fluorine‐18 Radiolabeling of Non‐Activated Arenes: From Concept to Clinical Research. The Chemical Record (2023).
5. A Design of Experiments (DoE) Approach Accelerates the Optimization of Copper-Mediated 18F-Fluorination Reactions of Arylstannanes. Scientific Reports (2019).
6. Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination. Scientific Reports (2017).