Modeling strategies for quantification of in vivo 18F-AV1451 binding in patients with tau pathology

27 October, 2016

Hahn A, Schain M, Erlandsson M, Sjölin P, James GM, Strandberg OT, Hägerström D,
Lanzenberger R, Jögi J, Olsson TG, Smith R, Hansson O

J Nuci Med.  2016 Oct 20. pii: jnumed.116.174508. [Epub ahead of print]

Abstract

Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer’s disease. In vivo imaging with positron emission tomography (PET) may offer important insights in pathophysiological mechanisms, diagnosis and disease progression. We describe different strategies for quantification of 18F-AV1451 (T807) tau binding, including models with blood sampling and non-invasive alternatives.

METHODS:

15 subjects (4 controls, 6 Alzheimer’s disease (AD), 3 progressive supranuclear palsy (PSP), 2 cortico basal syndrome (CBS)) underwent 180 min PET with 18F-AV1451 and arterial blood sampling. Modeling with arterial input functions included one-, two- and three-tissue compartment models and the Logan plot. Using cerebellum as reference region, the simplified reference tissue model 2 and Logan reference plot were applied. Finally, simplified outcome measures were calculated as ratio with reference to cerebellum concentrations (SUVR) and standard uptake values.

RESULTS:

Tissue compartment models were not able to describe the kinetics of 18F-AV1451 with poor fits in 33-53% of cortical regions and 80% in subcortical areas. In contrast, Logan plot showed excellent fits and parameter variance (VT standard error < 5%). Compared to the 180 min arterial-based Logan model, strong agreement was obtained for the Logan reference plot also for reduced scan time of 100 min (R2 = 0.91) and SUVR 100-120 min (R2 = 0.94), with 80-100min already representing a reasonable compromise between duration and accuracy (R2 = 0.93). Time activity curves and kinetic parameters were equal for cortical regions and the cerebellum in control subjects, but different in the putamen. Cerebellar total volumes of distribution were higher in controls than patients. For the above methods, increased cortical binding was observed for AD patients and to some extent for CBS, but not PSP.

CONCLUSION:

Using arterial input functions, the Logan plot provided the best estimate of tau binding. Assuming that cerebellum is a valid reference region, simplified methods seem to provide robust alternatives for quantification, such as the Logan reference plot with 100 min scan time. Furthermore, SUVR ratios between target and cerebellar activities obtained from a 80-100 min static scan offer promising potential for clinical routine application.

KEYWORDS:

Neurology; PET; Radiotracer Tissue Kinetics; kinetic modeling; positron emission tomography; quantification; tau imaging