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

Abstract

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 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 [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 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 [¹¹C]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 [¹⁸F]MK6240 correlated strongly and overall agreed well with those obtained from [¹¹C]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 [¹⁸F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [¹⁸F]MK6240 dynamic acquisition may thus offer complementary information about the pathophysiologic mechanisms of the disease.

Keywords: Alzheimer’s disease; PET imaging; [18F]MK6240; cerebral perfusion.