ABSTRACTBackgroundNeuroinflammation is proposed to accompany, or even contribute to, neuropathology in Friedreich ataxia (FRDA), with implications for disease treatment and tracking.ObjectivesTo examine brain glial activation and systemic immune dysfunction in people with FRDA and quantify their relationship with symptom severity, duration, and onset age.MethodsFifteen individuals with FRDA and 13 healthy controls underwent brain positron emission tomography using the translocator protein (TSPO) radioligand [18F]‐FEMPA, a marker of glial activation, together with the quantification of blood plasma inflammatory cytokines.Results[18F]‐FEMPA binding was significantly increased in the dentate nuclei (d = 0.67), superior cerebellar peduncles (d = 0.74), and midbrain (d = 0.87), alongside increased plasma interleukin‐6 (IL‐6) (d = 0.73), in individuals with FRDA compared to controls. Increased [18F]‐FEMPA binding in the dentate nuclei, brainstem, and cerebellar anterior lobe correlated with earlier age of symptom onset (controlling for the genetic triplet repeat expansion length; all rpart < −0.6), and in the pons and anterior lobe with shorter disease duration (r = −0.66; −0.73).ConclusionsNeuroinflammation is evident in brain regions implicated in FRDA neuropathology. Increased neuroimmune activity may be related to earlier disease onset and attenuate over the course of the illness. © 2021 International Parkinson and Movement Disorder Society

01 Mar 2015·European Journal of Nuclear Medicine and Molecular Imaging

Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer’s disease patients and control subjects

Article

Author: Merja Haaparanta-Solin ; Eugenii A. Rabiner ; Olof Solin ; Andrea Thiele ; Lutz Lehmann ; Tobias Heinrich ; Agneta Nordberg ; Lisa A. Wells ; Sonja Vollmer ; Akihiro Takano ; Christer Halldin ; Nabil Al-Tawil ; Andrea Varrone ; Marcus Schultze-Mosgau ; Vesa Oikonen ; Ray Valencia ; Anton Forsberg ; Juho Joutsa ; Sangram Nag ; Juha O. Rinne ; Anja Hoffmann ; Thomas Dyrks ; Ryuji Nakao

PURPOSEImaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer's disease (AD). [(18)F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [(18)F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [(18)F]FEMPA binding in AD patients than in controls could be detected in vivo.METHODSTen AD patients (five men, five women; age 66.9 ± 7.3 years; MMSE score 25.5 ± 2.5) and seven controls (three men, four women; age 63.7 ± 7.2 years, MMSE score 29.3 ± 1.0) were studied using [(18)F]FEMPA at Turku (13 subjects) and at Karolinska Institutet (4 subjects). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [(3)H]PK11195 in seven controls and eight AD patients. Cortical and subcortical regions of interest were examined. Quantification was performed using a two-tissue compartment model (2TCM) and Logan graphical analysis (GA). The outcome measure was the total distribution volume (V T). Repeated measures analysis of variance was used to assess the effect of group and TSPO binding status on V T.RESULTSFive AD patients and four controls were high-affinity binders (HABs). Three AD patients and three controls were mixed-affinity binders. V T estimated with Logan GA was significantly correlated with V T estimated with the 2TCM in both controls (r = 0.97) and AD patients (r = 0.98) and was selected for the final analysis. Significantly higher V T was found in the medial temporal cortex in AD patients than in controls (p = 0.044) if the TSPO binding status was entered as a covariate. If only HABs were included, significantly higher V T was found in the medial and lateral temporal cortex, posterior cingulate, caudate, putamen, thalamus and cerebellum in AD patients than in controls (p < 0.05).CONCLUSION[(18)F]FEMPA seems to be a suitable radioligand for detecting increased TSPO binding in AD patients if their binding status is taken into account.

100 Deals associated with [18F]FEMPA

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Plaque, Atherosclerotic	Preclinical	Finland	University of Turku	25 May 2016
Plaque, Atherosclerotic	Preclinical	Germany	Piramal Imaging GmbH	25 May 2016
Plaque, Atherosclerotic	Preclinical	Germany	Bayer Pharma AG	25 May 2016

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

[18F]FEMPA

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation