Abstract
Purpose[18F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [18F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [18F]flortaucipir with the novel tau tracer [18F]RO948 head-to-head in vivo.MethodsWe included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [18F]flortaucipir (80–100 min) and [18F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region.ResultsNeocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [18F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [18F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [18F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [18F]flortaucipir SUVR over the scanning interval, compared with a plateau for [18F]RO948.Conclusion[18F]RO948 and [18F]flortaucipir bound comparably in neocortical regions, but [18F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with [18F]RO948, compared with previous tau ligands.
Highlights
Alzheimer’s disease is characterized neuropathologically by the gradual deposition of amyloid-β (Aβ) into senile plaques and the aggregation of hyperphosphorylated tau into neurites and intrasomal neurofibrillary tangles [1, 2]
When examining Standardized uptake value ratios (SUVRs) over the full 100-min interval, SUVR values for [18F]flortaucipir appeared to continuously increase over time, in contrast to those for [18F]RO948, which reached a plateau during the scanning period
Strong correlations were observed between regional SUVR and DVR data for both tracers in the two patients depicted in Fig. 1 exhibiting more substantial tau pathology ([18F]flortaucipir, R2 = 0.978 and 0.988, P < 0.001; [18F]RO948, R2 = 0.991 and 0.998, P < 0.001)
Summary
Alzheimer’s disease is characterized neuropathologically by the gradual deposition of amyloid-β (Aβ) into senile plaques and the aggregation of hyperphosphorylated tau into neurites and intrasomal neurofibrillary tangles [1, 2]. The tau pathology associated with Alzheimer’s disease mainly consists of paired helical filaments (PHFs), formed by a mixture of three- and four-repeat tau isoforms [3]. This tau pathology is closely related to measures of neurodegeneration such as decreased glucose metabolism [4, 5] and to the development of cognitive symptoms [6,7,8]. In vivo, [18F]flortaucipir retention has been shown to correlate well with post mortem tau pathology in MAPT R406W mutation gene carriers [21] and to Alzheimer’s disease-related tau pathology [22]. [18F]flortaucipir performs excellently in distinguishing AD from other neurodegenerative disorders based on retention of the tracer in the temporal cortex [23]
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