[ ¹¹ C] (R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen’s encephalitis

Abstract

This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)-PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.

Positron Emission Tomography Imaging of Neuroinflammation

“…31 However, the high-resolution (photoemulsion) autoradiographic binding pattern in the demyelinated areas shows a different, less dense and obvious localization of the silver grains to astrocytic processes compared with the high background signal and the high density seen on activated microglia. 21 Labeled 32 Likewise, there is little binding of (R)-PK11195 in surgically removed tissue of hippocampal sclerosis. Where any binding has been seen, it appears to be on activated microglia lying amid the astrogliotic scar tissue.…”

Evaluation of Methods for Generating Parametric (R)-[11C]PK11195 Binding Images

“…Both uptake normalised to a reference region (Groom et al, 1995;Versijpt et al, 2003;Debruyne et al, 2003) and the simplified reference tissue model (SRTM) (Lammertsma and Hume, 1996) have been used (Cagnin et al, 2001a;Gerhard et al, 2003Gerhard et al, , 2004Gerhard et al, , 2005Gerhard et al, , 2006Turner et al, 2004). In some studies, the cerebellum was used as a reference tissue (Groom et al, 1995;Banati et al, 1999;Goerres et al, 2001;Gerhard et al, 2005); in others, a cluster analysis approach was adopted to define the normal reference region (Banati et al, 2000;Cagnin et al, 2001aCagnin et al, , c, 2004Gerhard et al, 2003Gerhard et al, , 2005Gerhard et al, , 2006Turner et al, 2004).…”

Proportion of infiltrating IgG-binding immune cells predict for tumour hypoxia

“…Non-invasive methods of detecting tumour hypoxia using MRI, EPR and PET are currently in development (Aboagye et al, 1998;O'Hara et al, 1998;Evans et al, 2000). PK11195, for example, binds to activated macrophages (Zovala and Lenfant, 1987), and PET studies using 11 C-PK11195 at Hammersmith hospital are being conducted to image macrophage infiltration during neuro-inflammation in Rasmussen's encephalitis (Banati et al, 1999); thus it may be possible to utilize this imaging approach to indirectly measure tumour hypoxia in addition to macrophage activation states. Furthermore, macrophage measurement may evade the potential risks associated with many conventional nitroimidazole-based hypoxic markers, which can have mutagenic and carcinogenic effects (Voogd, 1981;Tocher, 1997).…”