Brain inflammation, a hallmark of neurodegeneration and a potentially important therapeutic target, can be measured in vivo with translocator protein 18 kDa (TSPO) PET. Tracers bind to glia and peripherally-derived macrophages. ¹¹C-PBR28 and ¹¹C-ER176 “second-generation" tracers have high TSPO affinity, with ¹¹C-ER176 allowing for the study of all TSPO rs6971 genotypes. To assess their anatomical specificity, we used ¹¹C-PBR28 PET and ¹¹C-ER176 PET in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) respectively.

To determine whether brain inflammation positron emission tomography (PET) is anatomically specific for the various diseases causing dementia.

We studied 93 patients and 37 cognitively unimpaired healthy controls. Eighteen non-fluent primary progressive aphasia (nfvPPA) (age 67±6.3 years, 11/18 women), 12 semantic variant (svPPA) (65±7.6 years, 7/12 women), 10 behavioral variant (bvFTD) (63±8.1 years, 5/10 women) and 14 controls (68±6.1 years, 5/14 women) patients had ¹¹C-PBR28 PET. Fifty-three AD patients (age 67±9.2 years, 27/53 women) and 23 controls (68±6.1 years, 12/23 women) had ¹¹C-ER176 PET. Tracer uptake, V_T, values for ¹¹C-PBR28 and ¹¹C-ER176 were calculated with the Logan plot and a metabolite-corrected arterial input function. All images were corrected for partial volume effect. A full factorial analysis was performed on V_T values between patients and controls at the voxel level.

V_T values were increased (p < 0.005) in areas neuropathologically known to be maximally involved in each one of the FTLD variants and in AD, as follows: nfvPPA (L>R lateral premotor area, precentral gyrus, supplementary motor area (SMA), preSMA), svPPA (left temporal lobe, right temporal pole, left insula), bvFTD (both frontal lobes, anterior temporal lobes, insulae) and AD (precuneus and lateral temporal and parietal association cortex). In AD, inflammation topography correlated best with tau topography. 

TSPO PET is highly anatomically specific in FTLD and AD, providing a biomarker of brain inflammation, a potential therapeutic target in these conditions.