The primary goal of this study was to assess the suitability of ¹¹C-Pittsburgh compound B (¹¹C-PiB) blood–brain barrier delivery (K₁) and relative delivery (R₁) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of ¹¹C-PiB retention (amyloid-β load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, ¹⁵O-water PET, and ¹¹C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time–activity curves. Multiple analysis approaches provided regional ¹⁵O-water and ¹¹C-PiB measures of delivery and ¹¹C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial- and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., ¹⁵O-water K₁ and ¹¹C-PiB K₁, relative K₁ normalized to cerebellum [Rel-K_1-Water and Rel-K_1-PiB], and ¹¹C-PiB SRTM2-R₁) and between delivery measures and ¹¹C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (ρ ≈0.2–0.5) between ¹⁵O-water K₁ and ¹¹C-PiB K₁ that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K_1-Water and Rel-K_1-PiB and between Rel-K_1-Water and ¹¹C-PiB SRTM2-R₁ (ρ ≈0.5–0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between ¹¹C-PiB retention and relative ¹¹C-PiB delivery measures (but not ¹⁵O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: ¹¹C-PiB SRTM2-R₁ is highly correlated with regional relative CBF, as measured by ¹⁵O-water K₁ normalized to cerebellum, and cross-sectional ¹¹C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-β load and relative CBF) through dynamic ¹¹C-PiB imaging.

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