Quantitative Measurement of Tau Burden in a Dual-Time-Window Dynamic PET Imaging Protocol with [¹⁸F]MK6240

This study aimed to test and validate a dual-time-window (DTW) protocol for 6-(fluoro-¹⁸F)-3-(¹H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([¹⁸F]MK6240) dynamic PET imaging in experimental datasets acquired in human subjects. Methods: DTW protocols were tested and validated in datasets previously collected in 25 participants: 13 were cognitively normal, 10 had mild cognitive impairment, and 2 had Alzheimer disease. Participants underwent full 120-min [¹⁸F]MK6240 dynamic PET scans as well as structural MRI. Intermediary 3-dimensional volumes were removed from the acquired dynamic PET images to emulate DTW acquisitions consisting of an early phase and a late phase. Five break durations (30, 40, 50, 60, and 70 min) were investigated to determine the optimal break for 2 study durations (120 and 110 min). Regional brain time-activity curves were extracted using atlases available in the Montreal Neurologic Institute template space and using the FreeSurfer parcellation. Interpolation strategies were tested to recover the missing time points. Distribution volume ratio (DVR) estimates obtained from the DTW time-activity curves were compared with those obtained from the full time-activity curves as reference. Parametric maps were generated for the selected protocol and evaluated. Results: The correlation and agreement between DVR values obtained from the DTW method and the full time-activity curves were overall very good. The DTW protocol with a 60-min break using a biexponential model fit as the interpolation method provided the best compromise between practicality and quantitative accuracy. The mean differences between this DTW and the full acquisition, averaged across brain regions and all subjects, were less than 1% with a corresponding SD of less than 4%, and DVR estimates were not statistically different from those obtained from the full acquisition (P > 0.05). DVR parametric images were visually and quantitatively consistent with those obtained from the full acquisition. Conclusion: This study presents strong support for the use of a DTW protocol with [¹⁸F]MK6240. Such a protocol would be well suited to allow for both quantification of tau and derivation of an index of cerebral perfusion while reducing patient discomfort and increasing scanning efficiency in comparison to a full dynamic acquisition.