The high‐affinity peripheral benzodiazepine receptor ligand [11C]DAA1106 can be used to image microglia in animal models of Parkinson's disease and neuroinflammation in vivo using PET.

Abstract

Activated microglia are an important feature of several neurological diseases. We propose that activated microglia can be imaged using Positron Emission Tomography (PET) by taking advantage of elevated levels of peripheral benzodiazepine receptors (PBR) on activated microglia. We tested the hypothesis that DAA1106, a novel high‐affinity ligand to PBR, will specifically label activated microglia in vivo using PET. [3H]DAA1106 showed significantly higher binding in brain tissues in rats injected intrastriataly with either 6‐hydroxydopamine (6‐OHDA) or lipopolysaccaride (LPS) at the site of lesion. Immunohistochemistry combined with autoradiography in lesioned rats as well as cell cultures showed increased [3H]DAA1106 binding corresponding to activated microglia. PET imaging in vivo showed greater retention [11C]DAA1106 at the site of lesion in animals injected with either LPS or 6‐OHDA. Finally, DAA1106 showed higher affinity binding when compared to the well‐characterized PBR PET ligand PK11195 in both brain tissues and in vivo. These results indicate that DAA1106 binds with high affinity to microglia in neuroinflammatory disorders.