First PET scan for TB could improve treatment

A groundbreaking method for scanning tuberculosis (TB) has been innovated by researchers from the UK and the US, harnessing the capabilities of positron emission tomography (PET). This international team, including members from the Rosalind Franklin Institute, the Universities of Oxford and Pittsburgh, and the National Institutes of Health in the USA, has developed a novel radiotracer that targets live TB bacteria within the body.

This new radiotracer, named FDT, marks a significant advancement in TB diagnostics. Radiotracers are radioactive substances that emit radiation, which can be captured by PET scanners to produce detailed 3D images. FDT's development allows for the first time, PET scans to accurately identify the presence and activity of TB in a patient's lungs.

The team's research, funded by the Gates Foundation and UK Research and Innovation and published in Nature Communications, has progressed through rigorous pre-clinical trials with no adverse reactions, paving the way for Phase I human trials.

Currently, TB diagnosis relies on two primary methods: analyzing a patient's sputum for TB bacteria or employing PET scans to detect lung inflammation using the common radiotracer FDG. However, these methods have significant limitations. Sputum tests can return negative results even when the disease persists in the lungs, potentially leading to premature cessation of treatment. Inflammation-based scans, while useful in assessing disease extent, are not specific to TB and can produce misleading results as inflammation may be caused by other conditions and can persist even after the bacteria have been eradicated.

The new strategy developed by the research team offers a more precise diagnosis by utilizing a carbohydrate that is exclusively processed by TB bacteria. This specificity makes the new method a substantial improvement over existing techniques.

A notable advantage of this new approach is that it only necessitates standard radiation control and PET scanning equipment, which are increasingly accessible worldwide. The new radiotracer, FDT, is derived from FDG through a straightforward process involving enzymes developed by the researchers. This production method does not require specialized expertise or facilities, making it feasible for application in low- and middle-income countries, which bear over 80% of global TB cases and fatalities.

In 2021, TB afflicted 10.6 million individuals and caused 1.6 million deaths, ranking it as the second deadliest infectious disease after COVID-19.

Professor Ben Davis, Science Director of the Franklin's Next Generation Chemistry group, who spearheaded the research, emphasized the importance of accurately identifying active TB in the body. This accuracy is crucial not only for the initial diagnosis but also to ensure patients receive antibiotics for an adequate duration to fully eradicate the disease. The ability to send FDG and the necessary enzymes by post, combined with minimal additional training, means this diagnostic method can be implemented globally, especially in areas hardest hit by TB.

Dr. Clifton Barry III from the National Institute of Allergy and Infectious Diseases highlighted the practical benefits of FDT. He pointed out that FDT allows real-time assessment of TB bacteria viability in patients undergoing treatment, enabling faster and more effective clinical trials of new drugs. This real-time capability could drastically transform TB drug testing and clinical use, offering a significant leap forward in combating this deadly disease.