[ ¹¹ C]( R )-PK11195 PET imaging of microglial activation in multiple system atrophy

Abstract

Microglia, the brain's intrinsic macrophages, bind (R)-PK11195 when activated by neuronal injury. The authors used [11C](R)-PK11195 PET to localize in vivo microglial activation in patients with multiple system atrophy (MSA). Increased [11C](R)-PK11195 binding was primarily found in the dorsolateral prefrontal cortex, putamen, pallidum, pons, and substantia nigra, reflecting the known distribution of neuropathologic changes in MSA. Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA.

Quantitative Analysis for Estimating Binding Potential of the Peripheral Benzodiazepine Receptor with [11C]DAA1106

“…Although there was no significant difference among regions, the thalamus had the highest BP value. This observation is consistent with the BP value reported with [ 11 C]PK11195 (Groom et al, 1995;Cagnin et al, 2001;Gerhard et al, 2003). In [ 11 C]PK11195 PET studies, the semiquantification of specific binding was performed using late images, in which the activity of the region of interest was normalized to that of the cerebellum (Groom et al, 1995), cortical gray matter (Debruyne et al, 2003), or the whole brain (Debruyne et al, 2002).…”

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

“…The cerebellum has been used previously (Groom et al, 1995;Banati et al, 1999;Versijpt et al, 2003;Gerhard et al, 2005a), while an unaffected region was chosen to approximate those areas that would be found by cluster analysis as used in several reports (Banati et al, 2000(Banati et al, , 2001Cagnin et al, 2001a, b;Gerhard et al, 2003;Turner et al, 2004). Both these reference regions might, however, not be 'perfect' as reference tissue, because increased specific binding in these structures cannot be excluded.…”

“…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.…”