Reproducibility of [18F]MK-6240 kinetics in brain studies with shortened dynamic PET protocol in healthy/cognitively normal subjects.

Abstract

Background: [¹⁸F]MK-6240 is a neurofibrillary tangles PET radiotracer that has been broadly used in aging and Alzheimer's disease (AD) studies. Majority of [¹⁸F]MK-6240 PET studies use dynamic acquisitions longer than 60 min to assess the tracer kinetic parameters. As of today, no consensus has been established on the optimum dynamic PET scan time. In this study, we assess the reproducibility of [¹⁸F]MK-6240 quantitative metrics using shortest dynamic PET protocols in cognitively normal subjects. PET metrics were measured through two-tissue compartment model (2TCM) and Logan model to estimate VT and DVR, as well as SUVR from 90 to 120 min (SUVR_{90 - 120 min}) post-tracer injection for brain regions. 2TCM was carried out using the 120 min dynamic coffee break dataset (first scan from 0 to 60 min p.i., second scan from 90 to 120 min p.i.) and then repeated after stepwise shortening it by 5 min. The dynamic scan length that reproduced the 120 min dynamic scans-based VT to within 10% error was defined as the shortest acquisition time (SAT). The SAT SUVR_{90 - 120 min} was deduced from the SAT dataset by extrapolation of each image pixel time-activity curve to 120 min. The reproducibility of the 120 min dynamic scans-based VT_2TCM, DVR_2TCM, DVR_Logan, and SUVR using the SAT was assessed using Passing-Bablock analysis. The limits of reproducibility of each PET metrics were determined using Bland-Altman analysis.

Results: A dynamic SAT of 40 min yielded < 10% error in [¹⁸F]MK-6240 VT_2TCM's for all brain regions, compared to those measured using the 120 min datasets. SAT-based analysis did not show statistically significant systemic or proportional biases in VT_2TCM, DVR_2TCM, DVR_Logan, or SUVR compared to those deduced from the full dynamic dataset of 120 min. A mean difference between the 120 min- and SAT-based analysis of less than 4%, 10%, 15%, and 20% existed in the VT_2TCM, DVR_2TCM, DVR_Logan, and SUVR respectively.

Conclusion: Kinetic modeling of [¹⁸F]MK-6240 PET can be accurately performed using dynamic scan times as short as 40 min. This can facilitate studies with [¹⁸F]MK-6240 PET and improve patients accrual. Further work would be necessary to confirm the reproducibility of these results for patients in dementia spectra.