In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer’s disease patients

Purpose Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer’s disease (AD). (( R )-1-(2-chlorophenyl)- N -[ 11 C]-methyl- N -(1-methylpropyl)-3-isoquinoline caboxamide ([ 11 C]-( R )-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N -(5-fluoro-2-phenoxyphenyl)- N -(2-[ 18 F]fluoroethyl-5-methoxybenzyl)acetamide ([ 18 F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding. The aim of this study was to quantify in vivo binding of [ 18 F]FEDAA1106 to TSPO in control subjects and AD patients. Methods Seven controls (five men, two women, age 68±3 years, MMSE score 29±1) and nine AD patients (six men, three women, age 69±4 years, MMSE score 25±3) were studied with [ 18 F]FEDAA1106. PET measurements were performed on an ECAT EXACT HR system (Siemens Medical Solutions) in two 60-min dynamic PET sessions with a 30-min interval between sessions. Arterial blood radioactivity was measured using an automated blood sampling system for the first 5 min and using manually drawn samples thereafter. Quantification was performed using both kinetic analysis based on a two-tissue compartment model and Logan graphical analysis. Outcome measures were total distribution volume ( V T ) and binding potential ( BP ND = k 3 / k 4 ). An estimate of nondisplaceable distribution volume was obtained with the Logan graphical analysis using the first 15 min of PET measurements ( V ND 1-15 min ). Binding potential ( BP ND ) was also calculated as: V T / V ND 1-15 min − 1. Results No statistically significant differences in V T, k 3 / k 4 or BP ND were observed between controls and AD patients. Conclusion This study suggests that TSPO imaging with [ 18 F]FEDAA1106 does not enable the detection of microglial activation in AD.