Abstract
6-(fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [(18)F]MK6240 can be used to provide a surrogate 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 [(18)F]MK6240 and [(11)C]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 [(18)F]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 tissue, K (1) (mL⋅cm(-3)⋅min(-1)), and the simplified reference tissue model 2 was investigated for noninvasive estimation of the relative delivery rate, R (1) (unitless). A head-to-head comparison with R (1) derived from [(11)C]PiB scans was performed. Grouped differences in R (1) were evaluated among CN, MCI, and AD subjects. Results: Regional K (1) values suggested a relatively high extraction fraction. R (1) estimated noninvasively from simplified reference tissue model 2 agreed well with R (1) calculated indirectly from the blood-based compartment modeling (r = 0.99; mean difference, 0.024 ± 0.027), suggesting that robust estimates were obtained. R (1) measurements obtained with [(18)F]MK6240 correlated strongly and overall agreed well with those obtained from [(11)C]PiB (r = 0.93; mean difference, -0.001 ± 0.068). Statistically significant differences were observed in regional R (1) measurements among CN, MCI, and AD subjects, notably in the temporal and parietal cortices. Conclusion: Our results provide evidence that the early phase of [(18)F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [(18)F]MK6240 dynamic acquisition may thus offer complementary information about the pathophysiologic mechanisms of the disease.