Test-retest performance of [ ¹⁸ F]MK-6240 tau burden and relative delivery indices in cognitively normal older...

Accurate interpretation of quantitative positron emission tomography (PET)outcomes hinges on understanding the test-retest variability (T-RT).Previous studies of the tau-PET ligand [¹⁸F]MK-6240 reported adequateT-RT performance of tau burden estimates over a short-term 21-day and over alonger-term 6-month T-RT period, primarily involving Alzheimer's disease(AD) and cognitively normal (CN) subjects, respectively. However, several T-RTcharacteristics have not yet been reported, particularly in older CN (oCN)subjects. Here, we investigate the short-term T-RT performance of dynamic[¹⁸F]MK-6240 outcomes in a group largely consisting of oCN. Wereport T-RT for uptake in potential reference regions, for extracerebraloff-target signal, and for estimates of tau burden and relative delivery indicesin tau-bearing target regions. Eight participants (7 oCN, 1 AD) underwentbaseline dynamic [¹⁸F]MK-6240 PET/MRI (Biograph mMR) and a retestfollow-up PET/MRI scan within approximately 3 weeks. T-RT was evaluated usingabsolute percentage differences and intraclass correlation coefficients (ICC) inthree groups of regions: (1) potential reference regions usingstandardized-uptake values 90-110 minutes post-injection(SUV_90-110); (2) target regions using SUV ratios(SUVR_90-110), distribution volume ratios (DVR), andrelative delivery (R₁); and (3) extracerebral region usingSUVR_90-110. A voxel-based partial volume correction (PVC)was applied. T-RT was evaluated with and without PVC. In oCN subjects, theSUV_90-110T-RT in the evaluated reference regions rangedfrom 6 to 11% (ICC > 0.9); target region T-RT was similar forSUVR_90-110(4-9%, ICC: 0.62-0.97), DVR(3-10%, ICC: 0.66-0.92), and R₁(3-14%, ICC:0.52-0.97). PVC had minimal impact on reference regionSUV_90-110T-RT, but increased target region T-RTvariability (SUVR_90-110: 10-26%; DVR: 6-22%;R₁: 4-20%). Extracerebral SUVR_90-110exhibited higher T-RT variability (~12%, ICC: 0.85) than other target regions(average 6%) and increased to ~15% after PVC. Our findings are consistent withprevious reports and provide further evidence of acceptable[¹⁸F]MK-6240 T-RT in low-signal oCN subjects. Our results suggest[¹⁸F]MK-6240 is suitable for detecting early tau deposition andlongitudinal changes over time, and further support the viability of[¹⁸F]MK-6240 R₁to evaluate longitudinal changes inperfusion. PVC increased T-RT variability in tau burden and R₁outcomes. Notably, the extracerebral signal exhibited higher T-RT variabilitythan other target and reference regions and may affect their signal.