HEAD-TO-HEAD IN VIVO COMPARISON OF TAU POSITRON EMISSION TOMOGRAPHY LIGANDS 18F-FLORTAUCIPIR AND 18F-RO948

Abstract

18F-Flortaucipir (FTP) is the most widely used PET ligand for the in vivo assessment of tau pathology. It binds to paired-helical filament tau and has been shown to be useful in the diagnosis of AD. However, off-target binding e.g. in the choroid plexus and the basal ganglia hamper accurate quantification of FTP in these and adjacent regions. Recently, several other tau PET ligands have been developed. Here, we compare 18F-FTP with the novel tau ligand 18F-RO948 head-to-head in vivo. Within this study, 33 individuals have undergone 18F-FTP PET at 80–100 min and 18F-RO948 at 70- 90 min post ligand injection. Four subjects have undergone dynamic scanning 0–100 min. Subject diagnoses were: 18 AD (Aβpositive), three MCI (Aβpositive), four Progressive Supranuclear Palsy patients, three with semantic variant Primary Progressive Aphasia, one Dementia with Lewy Bodies and four neurologically healthy controls (mean age 71.6 ± 8.2 y). The average time between PET scans was 21 ± 41 days. Standardized uptake value ratios (SUVR) were created using an inferior cerebellar reference region. The neocortical retention of the two radioligands was highly similar when assessed using SUVR-values. A small, but significant, increase in retention was found in the entorhinal cortex (Braak stage I-II) using 18F-RO948 (Figure 1). On visual inspection, 18F-RO948 uptake was substantially lower in the basal ganglia, the thalamus, and the choroid plexus, but not in the substantia nigra compared to 18F-FTP uptake (Figure 2). Statistical comparison confirmed significantly lower 18F-RO948 uptake in the choroid plexus and the basal ganglia (Figure 3). However, some cases exhibited strong 18F-RO948 signal in the skull or the meninges, which was not observed for 18F-FTP, and at a group level the skull/meningeal binding was significantly higher in the 18F-RO948 scans.