PET Reveals Inflammatory Cycle in the Brain
A PET radiotracer called carbon-11 PBR28 (C-11 PBR28) could be the key to understanding how best to treat certain dementias, multiple sclerosis, and other deadly diseases of the nervous system, according to researchers from Yale University.

Immune cells in the central nervous system call microglia can be activated to trigger neuroinflammation that leads to neurodegeneration. To study this inflammatory cycle, researchers used PET to measure activation of microglia by employing a molecule from E coli bacteria called lipopolysaccharide (LPS), which stimulates the immune system and is accompanied by C-11 PBR28. When injected, the radiotracer binds to translocator proteins expressed on activated microglia, representing areas of increased microglial activation before and after immune stimulation with LPS.

"This imaging technique could shed light on the immune dysfunction that underpins a broad range of neuroinflammatory diseases, such as Alzheimer's disease, depression, posttraumatic stress disorder, and addiction," says Christine Sandiego, PhD, lead author of the study and a researcher from the department of psychiatry at the Yale School of Medicine in New Haven, Connecticut. "This is the first human study that accurately measures this immune response in the brain. The discoveries made with this technique could contribute to promising new drug treatments."

The PET radiotracer C-11 PBR28 was administered to eight healthy men around the age of 25, give or take six years, followed by two separate PET scans on the same day for each subject before and after injection with LPS. Adverse symptoms were self-reported and blood samples were taken to assess levels of peripheral inflammation. Results of the study showed that administering LPS led to a substantial spike in the systemic inflammatory response and levels of reported sickness, and activated microglia in the central nervous system.

With further research, eventual drug therapies could potentially cut the activation of neurodegenerative microglia and encourage neuroprotective processes in the brain.