Breaking the Mold

Pulmonary aspergillosis, a disease caused by the Aspergillus fumigatus fungus, is dangerous in patients with compromised immune systems. It’s also notoriously difficult to diagnose; blood tests take time and resources, but lack sensitivity and specificity even under the auspices of skilled diagnosticians. Culturing the fungus from lung biopsies is no easier, as many patients are too fragile to undergo the procedure. Using these methods, diagnosis can take up to a week as physicians wait for results from specialist testing centers – and with the speed at which the disease can progress, this can be a dangerous delay. There’s a clear unmet need, and in a bid to address it, an international research group including Christopher Thornton of the University of Exeter, UK, has developed an accurate, sensitive test based only on readily available imaging techniques.

Thornton initially met his collaborators at a conference, where they began talking about the possibility of such a technique. Despite their enthusiasm, it was only when the European Union put out a specific funding call in the area of imaging technologies for rare disease diagnosis that they were able to acquire the finances and assemble a consortium with the requisite skills. Thornton says, “As is frequently the case in science, there was a degree of serendipity – right time, right place, right idea.” The group’s test involves radioactively labeling antibodies to the fungus in vivo, then using a combination of positron emission tomography (PET) and magnetic resonance (MR) imaging to visualize the infection (1). So far, the technique has shown good results in mice (see Figure 1). “The next step is to adapt the technology for detection of human invasive pulmonary aspergillosis. To this end, we have ‘humanized’ the antibody tracer and are currently working through the regulatory framework to allow us to conduct human clinical trials in two years’ time.”

Aspergillosis isn’t the end of the road for the test, either. By applying the right antibodies, it can be used to detect bacteria, viruses and even cancer cells. “At present, cancers are visualized using the radiopharmaceutical fludeoxyglucose (¹⁸F),” explains Thornton. “However, we have shown that ¹⁸F is not appropriate for infectious disease detection, as it can’t discriminate between different types of pathogen, or between pathogens and general inflammation of the lung. By using our antibody-guided PET/MR imaging approach, diseases caused by fungi, bacteria and viruses will be detected and differentiated with a much higher degree of accuracy than is currently possible.” Not only that, but they can be detected rapidly using tools already available in most hospitals – meaning that hopefully, patients will receive the right treatment faster. MS