Abstract
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Objectives [18F]T807 was recently developed for PET imaging of tau protein aggregates. Post-mortem studies implicate tau deposition in a range of neuropathologies including traumatic brain injury. Here we provide an initial description of [18F]T807 pharmacokinetics in blood and brain. We also report on [18F]T807 brain uptake in a subject with suspected chronic traumatic encephalopathy.
Methods A 32 year old male with history of head trauma stemming from profession in contact sports was enrolled. [18F]T807 was given by i.v. bolus in a 2 hour dynamic PET scan. Radioactivity concentration in venous whole blood and plasma was measured. Column-switching HPLC was used for plasma radiometabolite analysis. PET images were aligned to the subject’s MRI, which was warped to a standardized space.
Results Whole blood:plasma ratio was near unity at all time points (range 0.97-1.06, temporally uncorrelated: R2=0.006, p=0.88). Over 90% of plasma activity was attributable to unchanged [18F]T807 at 90 min. [18F]T807 plasma kinetics were fit by a biexponential (t1/2s: 2, 81 min); the slower component comprised 31% of the extrapolated integral. Plasma clearance was 44 ml/kg/hr. Brain PET curves had rapid peak (gray matter: SUV≥3 at 3 min; white matter: SUV≈1 sustained 3-10 min) and washout (75% reduction from peak at 60 min in g.m., 30% in w.m.). Uptake was diffuse with localized enhancement in the frontal lobe, especially in w.m. and predominantly in left hemisphere.
Conclusions [18F]T807 pharmacokinetics are consistent with a reversibly binding ligand suitable for accurate quantification with PET. Bilateral but asymmetric retention suggestive of tau accumulation was noted in a subject with prior head trauma. Additional scans are scheduled for assessment of kinetic modeling with arterial inputs and for quantitative application of [18F]T807 to investigate brain injury and other neurological disorders.