18F‐MK‐6240 Tau PET as a Biomarker for Chronic Traumatic Encephalopathy: Case Series of 10 Symptomatic Former National Football League Players

Background The pathognomonic lesion of chronic traumatic encephalopathy (CTE) is the perivascular deposition of neuronal phosphorylated tau (p‐tau). Patchy p‐tau deposits initially accumulate in frontotemporal cortices. Medial temporal lobes (MTL) become involved in late stage. Validated in vivo biomarkers for CTE p‐tau do not exist. 18 F‐MK‐6240 is a second‐generation tau PET ligand with improved imaging properties compared with first‐generation ligands, but its utility in CTE is unknown. We report initial results from an ongoing proof‐of‐concept study investigating MK‐6240 in people at risk for CTE. Method Ten older adult male symptomatic former National Football League (NFL) players completed tau (MK‐6240) and amyloid (florbetapir) PET imaging and neuropsychological testing. MK‐6240 data were acquired from 36 cognitively unimpaired males without traumatic brain injury history (but unknown contact sport history) from the Wisconsin Registry for Alzheimer’s Prevention (mean age=66.3, SD=6.3; mean MMSE=29.6, SD=0.5). Using cerebellar gray matter reference, 70‐90 min MK‐6240 SUVR images were created. W‐score (age‐adjusted z‐scores) maps were generated using the control data and thresholded at w>1.65 to visualize high binding voxels. Images and scatter plots of uptake in NFL players and controls were qualitatively assessed due to the small sample size. Results Sample characteristics are in Table 1 (age range:51‐72, 5/10 Black). All NFL players had a negative florbetapir PET. 9/10 were cognitively impaired, particularly in memory and executive functions ( Table 2 ). One former NFL player (case 4) had MTL MK‐6240 uptake greater than all controls, along with focal low intensity uptake in the superior frontal cortex ( Figure 1 ). Two NFL players (cases 6 and 9) had mildly elevated MTL MK‐6240 uptake, particularly in entorhinal cortex and parahippocampus, though similar binding was seen in some controls ( Figure 2 ). There was minimal MTL uptake in the remaining NFL players. Cortical uptake was complicated by contamination from off‐target meningeal binding. Conclusions Existing data suggests current radioligands (e.g., flortaucipir) developed for Alzheimer’s disease might have restricted utility to late stage CTE. This might be true for MK‐6240 and off‐target meningeal binding complicates detection of cortical p‐tau. Data collection is ongoing and the larger data set will inform on MK‐6240 as a biomarker for CTE.