PET in the characterization of immune diseases and development of therapeutics

The immune system is a complex network of cells, tissues and organs that protects the body against harmful pathogens. Characterization of the immune system is essential for understanding the complex interactions underlying pathophysiology and providing insights to enable therapeutic targeting for modern drug development. Tissue and peripheral sampling report on important biomarkers, but may not adequately sample complex, heterogeneous systemic diseases. Imaging has been extensively used in the study of immune diseases, largely relying upon structural measurements of disease manifestation (e.g. X-ray for joint space narrowing in rheumatoid arthritis). These measurements are downstream from drug action, offering no insight into the intricacies of the immune system. Molecular imaging, particularly through Positron Emission Tomography has the potential to map the immune system at the whole-body level, providing non-invasive, quantitative readouts. Adoption of PET clinically and for drug development purposes for studying immune processes has been limited to date, lagging use in neuroscience and oncology. Emerging technical developments are likely to create new opportunities for immune system monitoring: (i) A broad set of clinical probes to study immune cells and associated processes are in development, (ii) The advent of TotalBody PET able to capture high-sensitivity measurements from all tissues with reduced radiation dose burden. This review explores the potential applications of PET for immune drug development, the technology advancements and suggests how adoption barriers can be overcome. The immune toolset of the future will likely demand an integrated approach, using tissue and peripheral readouts combined with immune-specific imaging.