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Clinical Evaluation of 18F-PI-2620 as a Potent PET Radiotracer Imaging Tau Protein in Alzheimer Disease and Other Neurodegenerative Diseases Compared With 18F-THK-5351

Purpose PET is a useful tool for detecting the presence and extent of brain tau accumulation. However, most first-generation tau PET tracers are limited for high off-target binding and detection of tau in non-Alzheimer disease (AD). This study evaluated potential clinical applications of 18F-PI-2620 as a novel PET tracer with a high binding affinity for tau deposition in AD and non-AD tauopathies. Methods Twenty-six participants diagnosed with either mild cognitive impairment, probable AD, frontotemporal dementia, or parkinsonism, as well as healthy controls underwent a 60- to 90-minute brain PET scan after 7 mci (259 MBq) injection of 18F-PI-2620. Some participants had previous PET scans using 18F-THK-5351 or 18F-FP-CIT for dopamine transporter imaging. Results All participants showed no increase in off-target binding in basal ganglia on 18F-PI-2620 PET images, as noted for first-generation tau tracers. Aβ+ mild cognitive impairment or AD patients showed diverse cortical 18F-PI-2620 uptake in frontotemporoparietal cortex that correlated with Mini-Mental Status Examination (ρ = −0.692, P = 0.013). Aβ+ Parkinson disease with dementia and (Aβ unknown) primary progressive aphasia patients also showed increased 18F-PI-2620 uptakes in the frontotemporoparietal cortex. Patients with parkinsonism showed increased uptakes in the pallidum compared with Aβ− healthy controls (left: 1.41 ± 0.14 vs 1.04 ± 0.13, P = 0.014; right: 1.18 ± 0.16 vs 0.95 ± 0.07, P = 0.014). Conclusions 18F-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with Aβ+ AD and Aβ+ non-AD tauopathies. Furthermore, this study showed that “off-target” binding in the basal ganglia does not affect 18F-PI-2620.