Modeling Strategies for Quantification of In Vivo ¹⁸F-AV-1451 Binding in Patients with Tau Pathology

Abstract

Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer disease (AD). In vivo imaging with PET may offer important insights into pathophysiologic mechanisms, diagnosis, and disease progression. We describe different strategies for quantification of F-AV-1451 (T807) tau binding, including models with blood sampling and noninvasive alternatives. Fifteen subjects (4 controls, 6 AD, 3 progressive supranuclear palsy, 2 cortico basal syndrome) underwent 180-min PET with F-AV-1451 and arterial blood sampling. Modeling with arterial input functions included 1-, 2-, and 3-tissue-compartment models and the Logan plot. Using the cerebellum as reference region, we applied the simplified reference tissue model 2 and Logan reference plot. Finally, simplified outcome measures were calculated as ratio, with reference to cerebellar concentrations (SUV ratio [SUVR]) and SUVs. Tissue compartment models were not able to describe the kinetics of F-AV-1451, with poor fits in 33%-53% of cortical regions and 80% in subcortical areas. In contrast, the Logan plot showed excellent fits and parameter variance (total volume of distribution SE< 5%). Compared with the 180-min arterial-based Logan model, strong agreement was obtained for the Logan reference plot also for a reduced scan time of 100 min ( = 0.91) and SUVR 100-120 min ( = 0.94), with 80-100 min already representing a reasonable compromise between duration and accuracy ( = 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 these methods, increased cortical binding was observed for AD patients and to some extent for cortico basal syndrome, but not progressive supranuclear palsy. The Logan plot provided the best estimate of tau binding using arterial input functions. Assuming that the 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, SUVRs between target and cerebellar activities obtained from an 80- to 100-min static scan offer promising potential for clinical routine application.

Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

“…Tau-PET imaging was conducted 80-100 min after bolus injection of 18 F-Flortaucipir on a GE Discovery 690 PET scanner (General Electric Medical Systems, Milwaukee, WI, USA). Radiosynthesis and radiochemical purity for 18 F-AV1451 within the BioFINDER study have previously been described in detail 63 . The image data were processed by the BioFINDER imaging core using a pipeline developed at Lund University that was described previously 64 .…”

18F‐flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study

“…30,31 18 F-flortaucipir data were reconstructed and corrected for motion using site-specific protocols, and subsequent processing was done using Statistical Parametric Mapping 12 (SPM12) software except where otherwise noted. Briefly, 18 F-flortaucipir frames were realigned, averaged across the 80–100 min time window, and coregistered to each subject’s T1-weighted MRI.…”

Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

“…BioFINDER cohort Healthcare, Amsterdam, the Netherlands), respectively, as previously described 24,54 .…”