Researchers at Uppsala University have developed a promising new PET imaging method that could significantly improve the diagnosis of Alzheimer’s disease and other neurological conditions. The study was conducted in collaboration with Uppsala University Hospital.
Antibody-based positron emission tomography (PET) is considered a powerful tool for visualizing disease-related proteins in the brain. However, its clinical use has been limited by two major challenges: difficulty in transporting antibodies across the blood–brain barrier and the need for long-lived radioactive tracers, which expose patients to radiation for extended periods.
‘Pretargeted’ PET using click chemistry
The Uppsala team has now demonstrated a novel “pretargeted PET” approach that addresses these limitations. Instead of attaching a radioactive tracer to the antibody from the outset, the method separates the process into two steps. The study was published in Translational Neurodegeneration.
First, an antibody tagged with a chemical marker is administered and allowed time to cross the blood–brain barrier and bind to its target, in this case amyloid beta, a protein strongly associated with Alzheimer’s disease. After several days, a small radioactive molecule is injected, which binds specifically to the tagged antibody through so-called “click chemistry.”
According to researcher Sara Lopes van den Broek, this approach avoids prolonged radiation exposure, as the radioactive component is only introduced once the antibody has reached its target. Professor Stina Syvänen describes the process as two “Lego bricks” that connect at the right moment, enabling precise imaging shortly after tracer administration.
More precise brain imaging
The study, conducted in mouse models, demonstrated that the method is feasible and can generate effective imaging signals. Importantly, the approach is not limited to Alzheimer’s disease. Because it targets proteins rather than specific conditions, it could be adapted for other neurological applications, such as brain tumors or neuroinflammatory diseases. The researchers are now focusing on optimizing the technique, including improving signal contrast and determining the optimal timing between antibody and tracer administration.
The ability to decouple antibody delivery from radioactive labeling represents a significant step forward in molecular imaging. By reducing radiation burden and enhancing targeting precision, pretargeted PET could expand access to advanced diagnostics and support earlier, more accurate detection of neurological diseases.
Further research will be required to validate the method in humans, but the findings highlight the potential of combining molecular biology and advanced imaging techniques to overcome longstanding barriers in brain diagnostics.
Alzheimer blood test
Last year, researchers developed a new blood test that showed strong potential for early and accessible diagnosis of Alzheimer’s disease. The test measures key biomarkers in blood plasma, including Aβ42/40 and p-tau217, which are associated with amyloid plaque formation. Notably, p-tau217 proved highly reliable in identifying Alzheimer’s-related memory problems.
Tested in over 500 patients, the approach offers a simpler, less invasive and more affordable alternative to PET scans and spinal taps. Researchers highlight its potential not only in clinical care but also in selecting and monitoring patients in clinical trials. Further validation is needed across diverse populations, but the findings underscore the growing role of blood-based biomarkers in advancing more accessible and patient-friendly dementia diagnostics.
