Wei Liu, a chemist at Virginia Tech, is leading new research that addresses a long-standing limitation in positron emission tomography (PET) imaging: how to reliably attach radioactive labels to complex molecules used as tracers in the body. The work, introduces a chemical method that expands the range of compounds that can be visualized with PET, with implications for medical diagnostics, drug development, and basic biological research.
Wang, C., DeMent, P., Jana, S., Hong, J., Pike, V. W., & Liu, W. (2025). Trifluoromethylation of alkyl electrophiles with 11 C- or 18 F-labeled fluoroform for PET applications. Science, 390(6779), 1278–1284. https://doi.org/10.1126/science.ady2969
PET imaging allows clinicians and researchers to observe biological processes in real time by tracking radiolabeled molecules as they move through tissues and organs. These tracer molecules are designed to interact with specific biological targets, such as tumors, receptors in the brain, or metabolic pathways in the heart. As the radioactive label decays, it emits signals that can be detected and reconstructed into detailed images of activity inside the body.
Wei Liu, a chemist at Virginia Tech stated,
“This can potentially revolutionize how the entire path and field develop tracer molecules for imaging important targets”.
Two radioisotopes dominate PET imaging: carbon-11 and fluorine-18. Carbon-11 closely mimics natural carbon in biological molecules, making it ideal for labeling drugs and biomolecules, but its short half-life of about 20 minutes limits how far it can be transported and how long imaging can last. Fluorine-18, with a half-life of roughly two hours, is far more practical for clinical use. However, incorporating fluorine-18 into complex molecules has proven difficult, restricting the types of tracers that can be made.
The Virginia Tech team focused on a common structural feature in modern pharmaceuticals known as the trifluoromethyl group. This chemical group is widely used in drug design because it can improve stability, binding strength, and how long a drug remains active in the body. Despite its importance, attaching fluorine-18 to trifluoromethyl groups in a reliable way has been a major challenge in radiochemistry.
Working with graduate student Chao Wang and collaborating with Victor Pike at the National Institute of Mental Health, Liu developed a method that uses copper as an intermediary to transfer radioactive fluorine into trifluoromethyl groups. The approach allows fluorine-18 to be incorporated into complex, drug-like molecules under conditions compatible with PET tracer production. Importantly, the same strategy can also be adapted to work with carbon-11, offering flexibility depending on the imaging need.
This advance builds on earlier efforts across the PET imaging field to improve labeling chemistry, but it stands out for its applicability to molecules that resemble real drugs rather than simplified test compounds. Independent reports covering the study have noted that many biological targets currently lack PET tracers not because they are unimportant, but because the chemistry required to label suitable molecules was not feasible. The new method directly addresses that gap.
From an engineering and translational research perspective, improved tracer labeling expands what PET imaging can measure. Researchers could design tracers that more closely match therapeutic drugs, enabling better tracking of how treatments distribute through the body or interact with their targets. In clinical settings, this could support earlier diagnosis, more precise monitoring of disease progression, and better assessment of treatment response.
The study also demonstrates progress toward more automated and reliable production of radiolabeled compounds, an important consideration given the time-sensitive nature of short-lived isotopes. Simplifying and standardizing tracer synthesis reduces barriers to adoption in hospitals and research centers that do not have extensive radiochemistry infrastructure.
While further validation and application-specific testing will be required, the work provides a new set of tools for PET tracer design. Rather than focusing on incremental improvements to existing tracers, the method opens access to a broader chemical space that was previously difficult to label. For Engineeringness readers, the significance lies in how a targeted advance in chemical engineering can unlock new capabilities in medical imaging, bridging fundamental chemistry with practical diagnostic technology.
Adrian graduated with a Masters Degree (1st Class Honours) in Chemical Engineering from Chester University along with Harris. His master’s research aimed to develop a standardadised clean water oxygenation transfer procedure to test bubble diffusers that are currently used in the wastewater industry commercial market. He has also undergone placments in both US and China primarely focused within the R&D department and is an associate member of the Institute of Chemical Engineers (IChemE).
