Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA

Abstract

One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18 kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [18F]-FEPPA. This study examined microglial activation as measured with [18F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19–82 years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [18F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [18F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [18F]-FEPPA VT (F (1,30) = 0.918; p = 0.346), and a significant effect of genetic polymorphism (F (1,30) = 8.767; p = 0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [18F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.

Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195

“…V T values of 11 C-PBR28 calculated by Logan analysis and 2TCM were highly correlated but seem less suitable as outcome parameters because of their high intersubject variability (Supplemental Table 1; Supplemental Fig. 1 [supplemental materials are available at http://jnm.snmjournals.org]) (14,28), which may be attributed to variations in the K 1 /k 2 (perfusion may be altered in neuroinflammatory processes) or to variations in plasma availability of 11 C-PBR28 (20). Consequently, V T comparison between groups was not performed in the current study.…”

Kinetic Modeling without Accounting for the Vascular Component Impairs the Quantification of [11C]PBR28 Brain PET Data

“…During the acquisition, blood samples (1.0 mL each) were drawn from the radial artery at 15-second intervals until 150 seconds, followed by 3 to 4.5-mL samples at 3,4,6,8,10,15,20,30,40,50,60,75,90, and 120 minutes. The plasma time-activity curve was corrected with the fraction of unchanged radioligand, as previously described.…”

“…9 However, genetic differences do not seem to account entirely for the substantial variability found in humans with these new inflammation ligands. A recent study failed to demonstrate increased neuroinflammation with aging 10 despite the fact that microglial activation is an aging hallmark. 11 Another study demonstrated lack of microglial activity in patients with mild depression.…”

In-vivo imaging of grey and white matter neuroinflammation in Alzheimer’s disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA

“…MRI acquisition parameters for both scanners have been described in detail elsewhere. 45 The PDweighted and T 2 FLAIR scans were visually inspected for evidence of focal and vascular lesions including the presence of white matter hyperintensities, which was determined by following established criteria. 46 The PET images were obtained for 125 min following the injection of [ 18 F]-FEPPA using a 3D high-resolution research tomograph brain tomograph (CS/Siemens, Knoxville, TN, USA) as previously described.…”