TSPO imaging in parkinsonian disorders

Gerhard, Alexander

doi:10.1007/s40336-016-0171-1

Cited by 55 publications

(33 citation statements)

References 51 publications

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“…The results from both the NY and BOS groups in this study showed that both the BP ND derived from the Super‐PK analysis as shown in Table and the V T based on the IDIF as shown in Table were higher in patients than controls. There were statistically significant differences between PD and HV in more regions than some studies, but not in as many as the other analytical methods . There were no differences in K 1 values observed between HV and PD groups at either the global or the regional level (see Fig ).…”

Section: Discussionmentioning

confidence: 67%

Noninvasive PK11195‐PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease

Kang

Mozley

Verma

et al. 2018

Journal of Neuroimaging

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BACKGROUND AND PURPOSENeuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11C](R)‐PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image‐derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug‐induced changes from system variance in longitudinal trials.METHODSThe sample consisted of 20 participants with PD and 19 HVs. Two independent teams analyzed the data to compare the volume of distribution calculated using image‐derived input functions (IDIFs), and binding potentials calculated using the Logan reference region model.RESULTSWith all methods, the higher signal‐to‐background in patients resulted in lower variability and better repeatability than in controls. We were able to use noninvasive techniques showing significantly increased uptake of PK in multiple brain regions of participants with PD compared to HVs.CONCLUSIONAlthough not necessarily reflecting absolute values, these noninvasive image analysis methods can discriminate between PD patients and HVs. We see a difference of 24% in the substantia nigra between PD and HV with a repeatability coefficient of 13%, showing that it will be possible to estimate responses in longitudinal, within subject trials of novel neuroprotective drugs.

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Section: Discussionmentioning

confidence: 67%

Noninvasive PK11195‐PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease

Kang

Mozley

Verma

et al. 2018

Journal of Neuroimaging

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“…There was high intersubject variability for regional BP values, a phenomenon that has been observed in other neurodegenerative disorders that have been examined with TSPO PET tracers. The high variability of microglial activation is also reflected in PET studies of idiopathic Parkinson's disease, with some authors finding a correlation with clinical phenotype, but others failing to do so . Because of the lack of TSPO studies in MSA, we can only assume at this stage that the clinical phenotype and severity will not be a simple linear function of the amount and localization of microglial activation.…”

Section: Discussionmentioning

confidence: 99%

Widespread microglial activation in multiple system atrophy

et al. 2019

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Background The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [ 11 C] (R) ‐PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients. Methods Fourteen patients with the parkinsonian phenotype of MSA (MSA‐P) with a mean disease duration of 2.9 years (range 2‐5 years) were examined with [ 11 C] (R) ‐PK11195 PET and compared with 10 healthy controls. Results Patients with the parkinsonian phenotype of MSA showed a significant ( P ≤ 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found. Conclusions In early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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“…pro versus antiinflammatory processes) and reactive astroglia have been shown to contribute to the TSPO PET signal, so further neurochemical and expression analyses would be needed to assess this (Lavisse et al, ). It is also possible that activated microglia vary in their protein expression profiles depending on their role in the various stages of neurodegeneration, which may complicate the association between increased TSPO binding and microglial activation (Gerhard, ). Finally, the expression of TSPO on blood vessel endothelium may also be a confounding factor (Turkheimer et al, ).…”

Section: Discussionmentioning

confidence: 99%

In vivo quantification of glial activation in minipigs overexpressing human α‐synuclein

Lillethorup

Glud

Landeck

et al. 2018

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Parkinson's disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson's disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [ C](R)PK11195, to image brain microglial activation and (+)-α-[ C]dihydrotetrabenazine ([ C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [ C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [ C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.

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TSPO imaging in parkinsonian disorders

Cited by 55 publications

References 51 publications

Noninvasive PK11195‐PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease

Noninvasive PK11195‐PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease

Widespread microglial activation in multiple system atrophy

In vivo quantification of glial activation in minipigs overexpressing human α‐synuclein

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