Thalamic microglial activation in ischemic stroke detected in vivo by PET and [ ¹¹ C]PK11195

Abstract

Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

Positron Emission Tomography Imaging of Neuroinflammation

“…18,29 A longitudinal [ 11 C](R)-PK11195 PET study in patients after ischemic stroke 59 demonstrated that [ 11 C](R)-PK11195 binding was present after the first week in the ischemic border zone, with an early detection beyond 72 hours, 60 and later spread beyond this region into the thalamus and neocortex. The later involvement in regions connected by degenerating white matter tracts to the ischemic core, such as the ipsilateral thalamus via the damaged corticothalamic projections, 61 was due to microglial activation occurring along the neuronal pathways expected to develop Wallerian degeneration and may have a role in long-term plasticity and recovery. 7 …”

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.…”

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

“…[ 11 C]PK11195 has been used for the in vivo imaging of PBR in the brain by positron emission tomography (PET), especially for the evaluation of lesions, and [ 11 C]PK11195 binding was reported to have increased in the stroke region (Pappata et al, 2000), plaque of multiple sclerosis (Banati et al, 2000;Debruyne et al, 2002), the cortex of Alzheimer's disease (Cagnin et al, 2001), and epileptic foci (Goerres et al, 2001). Since PBR localizes in glial cells in the brain, definition of the reference region without specific binding is difficult, especially in diseases with a widespread distribution of pathologic changes, such as Alzheimer's disease.…”