Single-tracer [¹⁸F]FDG PET quantification of blood-brain barrier permeability and cerebral blood flow: Validation...

Imaging the blood-brain barrier (BBB) permeability of molecular PET tracers may allow pathway-specific assessment of the diverse transport mechanisms expressed at the BBB. However, PET quantification of BBB permeability typically requires dual-tracer protocols involving a flow tracer, increasing methodological complexity and clinical burden. We evaluated a single-tracer dynamic PET method for quantifying the BBB permeability-surface area (PS) of [¹⁸F]fluorodeoxyglucose (FDG) against the conventional dual-tracer method. Our method uses high-temporal resolution imaging (1 s/frame), an image-derived arterial input function, and distributed kinetic modelling to simultaneously estimate cerebral blood flow (CBF) and transvascular transport rate K₁, from which BBB PS is calculated via the Renkin-Crone equation. Single-tracer and conventional dual-tracer PS estimates were compared in 18 volunteers scanned with the flow-tracer [¹¹C]butanol and [¹⁸F]FDG PET. Single-tracer [¹⁸F]FDG PS estimates had 3.7% mean bias and 4.2% standard deviation of differences compared to dual-tracer estimates. This was enabled by strong agreement between [¹⁸F]FDG and [¹¹C]butanol CBF estimates (Pearson R = 0.85, p < 0.001; mean difference: -0.057 ± 0.078 mL/min/cm³). These results demonstrate that high-temporal resolution dynamic PET enables single-tracer quantification of both CBF and BBB PS without a dedicated flow tracer, expanding opportunities for quantitative studies of molecular BBB transport across a broad range of tracers and disorders.