Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging

6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [18F]MK6240 can be used to provide a sur-rogate index of cerebral perfusion. Methods: Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [18F]MK6240 and [11C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information. Arterial blood samples were collected in a subset of 24 subjects for [18F]MK6240 scans to derive metabolite -corrected arterial input functions. Regional time-activity curves were extracted using atlases available in the Montreal Neurologic Institute template space and using FreeSurfer. The early phase of brain time- activity curves was analyzed using a 1-tissue-compartment model to obtain a robust estimate of the rate of transfer from plasma to brain tis-sue, K1 (mL & BULL;cm-3 & BULL;min-1), and the simplified reference tissue model 2 was investigated for noninvasive estimation of the relative delivery rate, R1 (unitless). A head-to-head comparison with R1 derived from [11C]PiB scans was performed. Grouped differences in R1 were evaluated among CN, MCI, and AD subjects. Results: Regional K1 values sug-gested a relatively high extraction fraction. R1 estimated noninvasively from simplified reference tissue model 2 agreed well with R1 calculated indirectly from the blood-based compartment modeling (r = 0.99; mean difference, 0.024 & PLUSMN; 0.027), suggesting that robust estimates were obtained. R1 measurements obtained with [18F]MK6240 corre-lated strongly and overall agreed well with those obtained from [11C]PiB (r = 0.93; mean difference, -0.001 & PLUSMN; 0.068). Statistically significant differences were observed in regional R1 measurements among CN, MCI, and AD subjects, notably in the temporal and parietal cortices. Conclusion: Our results provide evidence that the early phase of [18F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [18F]MK6240 dynamic acquisi-tion may thus offer complementary information about the pathophysio-logic mechanisms of the disease.

Automated summary

This study investigated the use of [18F]MK6240 to derive a useful index of cerebral perfusion. The results showed that early-phase brain images provided valuable information about cerebral perfusion and were highly consistent with [11C]PiB results. Therefore, both the early and late phases of [18F]MK6240 dynamic acquisition can offer complementary information about the pathophysiological mechanisms of the disease.