[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

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Abstract

Background

Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [ ¹¹C]-( R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [ ¹¹C]-( R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [ ¹¹C]-DPA-713 and [ ¹⁸F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.

Materials and Methods

Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [ ¹¹C]-( R)-PK11195, [ ¹¹C]-DPA-713, and [ ¹⁸F]-DPA-714.

Results

Uptake of [ ¹¹C]-DPA-713 in infected brain areas was comparable to that of [ ¹¹C]-( R)-PK11195, but [ ¹¹C]-DPA-713 showed lower non-specific binding. Non-specific uptake of [ ¹⁸F]-DPA-714 was lower than that of [ ¹¹C]-( R)-PK11195. In the infected brain, total [ ¹⁸F]-DPA-714 uptake was lower than that of [ ¹¹C]-( R)-PK11195, with comparable specific uptake.

Conclusions

[ ¹¹C]-DPA-713 may be more suitable for visualizing mild inflammation than [ ¹¹C]-( R)-PK11195. In addition, the fact that [ ¹⁸F]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting.

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Most cited references 27

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

Virginia F. J. Newcombe, Daniel Price, G Giovannoni … (2000)

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. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.

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Visualising microglial activation in vivo.

R Banati (2002)

In health, microglia reside as quiescent guardian cells ubiquitously, but isolated without any cell-cell contacts amongst themselves, throughout the normal CNS. In disease, however, they act as swift "sensors" for pathological events, including subtle ones without any obvious structural damage. Once activated, microglia show a territorially highly restricted involvement in the disease process. This property, peculiar to microglia, confers to them diagnostic value for the accurate spatial localisation of any active disease process, acute or chronic. In the brain, the isoquinoline PK11195, a ligand for the peripheral benzodiazepine binding site (PBBS), binds with relative cellular selectivity to activated, but not resting, microglia. Labelled with carbon-11, (R)-PK11195 and positron emission tomography (PET) have been used for the study of inflammatory and neurodegenerative brain disease in vivo. These studies demonstrate meaningfully distributed patterns of regional [(11)C](R)-PK11195 signal increases that correlate with clinically observed loss of function. Increased [(11)C](R)-PK11195 binding closely mirrors the histologically well-described activation of microglia in the penumbra of focal lesions, as well as in the distant, anterograde, and retrograde projection areas of the lesioned neural pathway. There is also some indication that in long-standing alterations of a neural network with persistent abnormal input, additional signals of glial activation may also emerge in transsynaptic areas. These data suggest that the injured brain is less static than commonly thought and shows subtle glial responses even in macroanatomically stable appearing regions. This implies that glial activation is not solely a sign of tissue destruction, but possibly of disease-induced adaptation or plasticity as well. Whilst further technological and methodological advances are necessary to achieve routine clinical value and feasibility, a systematic attempt to image glial cells in vivo is likely to furnish valuable information on the cellular pathology of CNS diseases and their progression within the distributed neural architecture of the brain. Copyright 2002 Wiley-Liss, Inc.

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Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study.

R Banati, Johannes Schwarz, Richard Wise … (2005)

We obtained [11C](R)-PK11195 PET scans in six patients at different time points between 3 and 150 days after onset of ischemic stroke in order to measure the time course of microglial activation. Increased [11C](R)-PK11195 binding around the lesion was observed as early as 3 days. Scans at later time points showed ongoing changes in the distribution of the [11C](R)-PK11195 signal, involving the area of the primary lesion and areas distant from the primary lesion site. Our data suggest that [11C](R)-PK11195 PET can be used to investigate both the primary lesion and remote pathological changes following Wallerian degeneration.

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Author and article information

Contributors

: +31-50-3613311 , +31-50-3611687 , j.doorduin@ngmb.umcg.nl

Journal

Journal ID (nlm-ta): Mol Imaging Biol

Title: Molecular Imaging and Biology

Publisher: Springer-Verlag (New York )

ISSN (Print): 1536-1632

ISSN (Electronic): 1860-2002

Publication date (Electronic): 28 March 2009

Publication date (Print): November 2009

Volume: 11

Issue: 6

Pages: 386-398

Affiliations

[1 ]Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

[2 ]University Center of Psychiatry, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

[3 ]Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050 Australia

[4 ]School of Chemistry, University of Sydney, Sydney, NSW 2006 Australia

[5 ]Discipline of Medical Radiation Sciences, University of Sydney, Sydney, NSW 2006 Australia

Article

Publisher ID: 211

DOI: 10.1007/s11307-009-0211-6

PMC ID: 2763079

PubMed ID: 19330384

SO-VID: 6a67eacc-1e07-43d9-b941-9944c681327f

History

Date received : 23 September 2008

Date revision received : 29 October 2008

Date accepted : 18 December 2008

Custom metadata

ScienceOpen disciplines: Molecular biology

Keywords: [11c]-pk11195,positron emission tomography,tspo,microglia,neuroinflammation

Data availability:

ScienceOpen disciplines: Molecular biology

Keywords: [11c]-pk11195, positron emission tomography, tspo, microglia, neuroinflammation