Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study

  title={Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study},
  author={Martin R. Turner and Annachiara Cagnin and Federico E. Turkheimer and Ccj Miller and Christopher E. Shaw and David J. Brooks and P. Nigel Leigh and Richard B. Banati},
  journal={Neurobiology of Disease},

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

It is suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease, which might improve the understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.

Brain Metabolism and Microglia Activation in Mild Cognitive Impairment: A Combined [18F]FDG and [11C]-(R)-PK11195 PET Study.

Microglia activation is present in the prodromal MCI phase of different underlying etiologies, showing spatial concordance and inverse correlation with brain glucose metabolism at single-subject level, suggesting a possible contribution of activated microglia to neurodegeneration, showing important implications for local immune activity in the early neurodegenersative processes.

Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?

A comprehensive review of PET studies investigating ALS and ALS-mimicking conditions, articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients are presented.

Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28

In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors

The new PBR ligand CLINME is described as an alternative to PK11195 and performs better than [11C]PK11195 in this model of local acute neuroinflammation and compared with the reference compound, using autoradiography and PET imaging.

Mills’ and other isolated upper motor neurone syndromes: in vivo study with 11C-(R)-PK11195 PET

It is concluded that Mills’ syndrome is a purely clinical description that should be reserved for patients with a progressive spastic hemiparesis for which no other explanation can be found.

Positron Emission Tomography Imaging of Neuroinflammation

It is proposed that PET imaging using [11C](R)PK11195 may be a valuable tool for detecting neuroinflammation in the brain of newborns born to mothers with chorioamnionitis.

Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

This study provides evidence for differences in the distribution of reduced cortical [11C]flumazenil binding in homD90A compared with sALS patients and hypothesize that this might reflect differences in cortical neuronal vulnerability.

In vivo evidence for microglial activation in neurodegenerative dementia

Some of the posited functions of activated microglia in the pathophysiology of dementia are reviewed and the relationship between increased regional [11C](R)‐PK11195 signals and the ensuing changes in brain volume is speculated on.

Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset

This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia.



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

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.

Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil.

Observations suggest that cerebral dysfunction in ALS involves motor/premotor and extramotor areas, particularly the prefrontal regions, which correlate closely with receptor density.

The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology.

In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion.

In vivo imaging of activated microglia/brain macrophages provides a dynamic measure of active tissue changes following an acute focal lesion, demonstrating that the glial tissue response in the wake of neuronal damage is protracted and widespread within the confines of the affected distributed neural system and can be related to the long-term functional deficits.

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

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.

Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study.

Focally impaired activation of the medial prefrontal cortex and parahippocampal gyrus in ALS patients during the process of internal generation of movement could underlie the frontal lobe cognitive deficits reported in previous neuropsychological studies of ALS.

PK (‘peripheral benzodiazepine’) – binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK 11195 binding to activated microglia

PK 11195 is a well-suited marker to detect microglial activation in areas of subtle brain pathology, where neither a disturbance of the blood–brain barrier function nor the presence of macrophages and inflammatory cells indicate an on-going disease process.

Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia.

The data provide evidence for a close link between neurodegeneration and the activation of microglia; a possible local antigen production againstmicroglia/brain macrophages, which might regulate the concomitant glial activation in Neurodegenerative diseases; and the presence of microGlia-binding cerebrospinal antibodies as a marker for the acuity of the disease process underlying the acute deterioration of the neurological and cognitive performance in patients with ALS.

Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

The results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients and suggest dysfunction of DLPFC in some ALS patients with associated cognitive impairments.