Clinical Evaluation of18F-PI-2620 as a Potent PET Radiotracer Imaging Tau Protein in Alzheimer Disease and Other Neurodegenerative Diseases Compared With18F-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(18)F-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(18)F-PI-2620. Some participants had previous PET scans using(18)F-THK-5351 or(18)F-FP-CIT for dopamine transporter imaging. Results All participants showed no increase in off-target binding in basal ganglia on(18)F-PI-2620 PET images, as noted for first-generation tau tracers. A beta+ mild cognitive impairment or AD patients showed diverse cortical(18)F-PI-2620 uptake in frontotemporoparietal cortex that correlated with Mini-Mental Status Examination (rho = -0.692,P= 0.013). A beta+ Parkinson disease with dementia and (A beta unknown) primary progressive aphasia patients also showed increased(18)F-PI-2620 uptakes in the frontotemporoparietal cortex. Patients with parkinsonism showed increased uptakes in the pallidum compared with A beta- 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 F-18-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with A beta+ AD and A beta+ non-AD tauopathies. Furthermore, this study showed that "off-target" binding in the basal ganglia does not affect(18)F-PI-2620.