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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 42; no. 3; pp. 438 - 446
• Main Authors: Varrone, Andrea, Oikonen, Vesa, Forsberg, Anton, Joutsa, Juho, Takano, Akihiro, Solin, Olof, Haaparanta-Solin, Merja, Nag, Sangram, Nakao, Ryuji, Al-Tawil, Nabil, Wells, Lisa A., Rabiner, Eugenii A., Valencia, Ray, Schultze-Mosgau, Marcus, Thiele, Andrea, Vollmer, Sonja, Dyrks, Thomas, Lehmann, Lutz, Heinrich, Tobias, Hoffmann, Anja, Nordberg, Agneta, Halldin, Christer, Rinne, Juha O.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2015; Springer Nature B.V
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer's disease; Cardiology; Dementia; Female; Humans; Hydrocarbons, Fluorinated - adverse effects; Hydrocarbons, Fluorinated - pharmacokinetics; Imaging; Ligands; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Middle Aged; Nuclear Medicine; Oncology; Original Article; Orthopedics; Positron-Emission Tomography; Protein Binding; Proteins; Pyridines - adverse effects; Pyridines - pharmacokinetics; Radiology; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - pharmacokinetics; Receptors, GABA - metabolism; Tomography; Neuroinflammation; Alzheimer; Translocator protein; Microglia; Dementia
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-014-2955-8

Purpose Imaging 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. Methods Ten 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 . Results Five 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.