Chronic microglial activation is an important component of many
neurological disorders, and imaging activated microglia in vivo will enable the detection and improved treatment of
neuroinflammation. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox-amide (
PK11195), a peripheral
benzodiazepine receptor ligand, has been used to image
neuroinflammation, but the extent to which
PK11195 binding distinguishes activated microglia and reactive astrocytes is unclear. Moreover,
PK11195 may lack sufficient sensitivity for detecting mild
neuroinflammation. We hypothesized that N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)
acetamide (
DAA1106), a new
ligand that binds specifically to peripheral
benzodiazepine receptor, binds to activated microglia in human neurological diseases with higher affinity than does
PK11195. We therefore compared the pharmacological binding properties of [3H](R)-
PK11195 and [3H]
DAA1106 in postmortem tissues from patients with
cerebral infarcts,
amyotrophic lateral sclerosis,
Alzheimer disease,
frontotemporal dementia, and
multiple sclerosis (n=10 each). In all diseases, [3H]
DAA1106 showed a higher binding affinity as reflected by lower dissociation constant (KD) values than that of [3H](R)-
PK11195. Moreover, specific binding of both
ligands correlated with the presence of activated microglia identified by immunohistochemistry in situ. We conclude that 1)
ligands that bind peripheral
benzodiazepine receptor mainly label activated microglia in human
neurological disorders and that 2)
DAA1106 may possess binding characteristics superior to those of
PK11195, which may be beneficial for in vivo positron emission tomography imaging.