In-vivo-Bildgebung „neuroinflammatorischer Veränderungen“ mit PET; Grundlagen und Anwendung bei Parkinson-Syndromen

Zusammenfassung

Mikroglia sind residente immunkompetente Zellen des Gehirns, die durch unspezifische Schädigung aktiviert werden. Im aktivierten Zustand exprimieren sie das „translocator protein 18 kD“ (TSPO) – früher peripherer Benzodiazepinrezeptor genannt, an welches hochspezifisch das Isoquinolin PK11195 bindet. Radioaktiv markiert kann das R-Enantiomer [¹¹C] PK11195 als Ligand in der Positronenemissionstomografie (PET) genutzt werden und ermöglicht so die in-vivo-Darstellung „aktiver“ neuroinflammatorischer Veränderungen.

Mit der [¹¹C](R) PK11195 PET konnte bisher in-vivo-Mikroglia-Aktivierung bei ischämischen (Schlaganfall), entzündlichen (Multiple Sklerose) und degenerativen (Morbus Alzheimer und Parkinson) Erkrankungen demonstriert werden. In der vorliegenden Kurzübersicht werden die Ergebnisse bei idiopathischen und atypischen Parkinson-Syndromen vorgestellt.

Zusätzlich wurden in den letzten Jahren neue, teilweise ¹⁸F-markierte PET-Liganden mit unterschiedlichen Bindungseigenschaften entwickelt, die z. T. in klinischen Studien evaluiert wurden.

Longitudinale Studien, kombiniert mit therapeutischer Intervention und neuropathologischer Evaluierung, werden helfen, die Beziehung von Lokalisation und Ausmaß der Mikroglia-Aktivierung zur klinischen Krankheitsausprägung zu explorieren.

Abstract

Microglia are the brain’s resident, immunocompetent cells that can be activated by unspecific (damaging) stimuli. In their activated state they express „translocator protein 18 kD“ (TSPO) – previously called the peripheral benzodiazepine binding site – which binds the isoquinolin PK11195 in a highly specific manner. When radioactively labelled the R-enantiomer [¹¹C] PK11195 can be used with Positron Emission Tomography (PET) to demonstrate neuroinflammatory changes in vivo.

So far [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) conditions.

This short review summarises the findings in idiopathic and atypical Parkinsonian syndromes.

Currently longitudinal studies are in progress to help clarifying the relationship between localisation and extent of microglial activation and the clinical findings in these disorders. This will assist to determine the role of [¹¹C](R) PK11195 PET as a diagnostic tool and a surrogate marker of “neuroinflammation” in therapeutic trials.

Schlüsselwörter

Parkinson-Syndrome - Mikroglia - Neuroinflammation - PET

Key words

Parkinson‘s Disease - microglia - neuroinflammation - PET

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