In-vivo-Darstellung „neuroinflammatorischer” Veränderungen mit [¹¹C] PK11195-PET

Zusammenfassung

Mikroglia sind residente immunkompetente Zellen des Gehirns, die durch akute, aber auch langsam voranschreitende, chronische Schädigungprozesse aktiviert werden. Im aktivierten Zustand exprimieren sie den peripheren Benzodiazepinrezeptor, an den das Isoquinolin PK11195 spezifisch bindet. Radioaktiv markiert kann das R-Enantiomer [¹¹C] PK11195 als Ligand in der Positronenemissionstomographie (PET) genutzt werden und ermöglicht so die In-vivo-Darstellung aktiver „neuroinflammatorischer”, d. h. die Mikroglia aktivierender, Veränderungen.
Mit der [¹¹C](R) PK11195-PET konnte bisher In-vivo-Mikrogliaaktivierung bei ischämischen (Schlaganfall), entzündlichen (multiple Sklerose) und degenerativen (Morbus Alzheimer- und Parkinson-Erkrankung) demonstriert werden. Laufende longitudinale Studien werden dazu beitragen, die Beziehung zwischen Lokalisation und Ausmaß der Mikrogliaaktivierung und klinischer Krankheitsausprägung näher zu bestimmen. Dies wird zeigen, welche Rolle [¹¹C](R) PK11195-PET als Surrogatmarker von „Neuroinflammation” in der Diagnose und in Therapiestudien zukommt.

Abstract

Microglia are the brains' resident immunocompetent cells that can be activated by acute as well as chronic pathological stimuli. When activated they express the peripheral benzodiazepine binding site to which the isoquinolin PK11195 binds with high specificity. Labelled with [¹¹C], the R-enatiomer [¹¹C] PK11195 has been used for Positron Emission Tomography (PET) studies to demonstrate neuroinflammatory changes in vivo.
[¹¹C](R) PK11195-PET has been successfully used to show in vivo microglial activation in ischemic (stroke), inflammatory (multiple sclerosis) and degenerative (Alzheimer's and Parkinson's disease). Longitudinal studies are in progress to help to clarify the relationship between localisation and extent of microglial activation and the clinical presentations in these disorders. This will help to determine the role of [¹¹C](R) PK11195 PET as a diagnostic tool and a surrogate marker of “neuroinflammation” in therapeutic trials.

Schlüsselwörter

Mikrogliaaktivierung - Neuroprotektion - PK11195 - Positronen-Emissions-Tomographie

Key words

Microglial activation - Neuroprotection - PK11195 - Positron emission tomography

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