In vivo imaging of microglial activation with [¹¹C](R)‐PK11195 PET in progressive supranuclear palsy

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss, associated with intracellular neurofibrillary tangles and activated microglia, is found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)-PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS) expressed by activated microglia. We have used [11C](R)-PK11195 PET to demonstrate in vivo the degree and distribution of the glial response to the degenerative process in four patients with PSP. Compared to normal age-matched controls, the PSP patient group showed significantly increased mean [11C](R)-PK11195 binding in the basal ganglia, midbrain, the frontal lobe, and the cerebellum. Two of the patients were rescanned after 6 to 10 months and during that time the level of microglial activation remained stable. [11C](R)-PK11195 PET reveals a pattern of increased microglial activation in PSP patients involving cortical and subcortical regions that corresponds well with the known distribution of neuropathological changes. [11C](R)-PK11195 PET, therefore, may help in characterizing in vivo the underlying disease activity in PSP.

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

“…Whereas results of previous PET studies using 11 C-PK11195 in Parkinson's disease showed increased binding in the midbrain 35 and different frontal and temporal cortical regions, 36 other reports did not identify major differences between binding in Parkinson's disease and controls. 37 Conversely, more consistent increases in 11 C-PK11195 binding have been reported in multiple systems atrophy, 38 progressive supranuclear palsy, 39 corticobasal degeneration, 40 and Huntington's disease. 41 Reasons for such variability could include limitations inherent to this particular tracer, such as high non-specific binding, low brainpenetration, high plasma-protein-binding, and difficult preparation.…”

Positron Emission Tomography Imaging of Neuroinflammation

“…Microglial activation has been demonstrated in vivo using [ 11 C](R)-PK11195 PET in the brains of patients with idiopathic PD 44,45 and atypical parkinsonism, such as multiple system atrophy, 46 progressive supranuclear palsy, 47 and corticobasalganglionic degeneration. 48 In these conditions, the distribution of [ 11 C](R)-PK11195 binding mirrors the spatial pattern of known distinct neuropathologic hallmarks.…”

Evaluation of Reference Tissue Models for the Analysis of [11C](R)-PK11195 Studies

“…Both [ 11 C](R)-PK11195 and [ 11 C]PK11195 have been used as positron emmision tomography (PET) tracers to study activated microglia in various neurologic disorders. It has been used to study stroke (Ramsay et al, 1992;Pappata et al, 2000;Gerhard et al, 2000Gerhard et al, , 2005a), Alzheimer's disease (Groom et al, 1995; Cagnin et al, 2001a;Versijpt et al, 2003), multiple sclerosis (Banati et al, 2000;Debruyne et al, 2002Debruyne et al, , 2003Versijpt et al, 2005) and various other diseases (Pappata et al, 1991; Banati et al, 1999Banati et al, , 2001Goerres et al, 2001;Cagnin et al, 2001bCagnin et al, , 2004Cicchetti et al, 2002;Gerhard et al, 2003Gerhard et al, , 2004Gerhard et al, , 2005bTurner et al, 2004Turner et al, , 2005Venneti et al, 2004;Henkel et al, 2004;Ouchi et al, 2005). Most studies have used a reference tissue approach to quantify binding, either by applying the simplified reference tissue model (SRTM) (Lammertsma and Hume, 1996) or by using uptake normalized to a reference region.…”