Active Delivery of Radiotracers Across the Blood Brain Barrier

Researchers at Stanford have developed an innovative in vivo imaging approach to detect inflammatory responses and monitor disease activity by leveraging immune cells that cross the blood brain barrier (BBB) during inflammation. They have demonstrated a PET radiotracer that binds to an antigen, e.g., TREM1 (Triggering Receptor Expressed on Myeloid Cells-1), on peripheral immune cells to facilitate active transport into the central nervous system (CNS). Peripheral immune cells can include myeloid cells, NK cells, macrophages, monocytes, granulocytes, dendritic cells and others that infiltrate the brain during inflammatory states such as in multiple sclerosis (MS) and other neurological diseases. The attached diagnostic agent can be used to track these cells and image their location in the CNS, thus identifying the location of an inflammation associated with disease. Additionally this peripheral targeting can be used to transport therapeutics into the brain to treat those areas of inflammation or pathology. Currently, delivering diagnostics and therapeutic molecules across the blood brain barrier (BBB) for detecting and treating neurological diseases remains challenging. Novel clinical imaging strategies that enable visualization of innate immune status in the CNS are essential to improve disease staging and therapeutic monitoring in patients with MS and other neurological diseases.

Stage of Development
The researchers have shown that TREM1-PET imaging has high potential for clinical translation to aid early diagnosis, accurate staging, and therapeutic monitoring in MS. Moreover, whole body imaging of maladaptive myeloid cell activation using TREM-1 PET has potential to shed light on the spatiotemporal dynamics of innate immune dysfunction in the whole body and brain across a broad range of diseases.