Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases

Abstract

Purpose In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). Methods Forty-nine participants were scanned with 18 F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. Results SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18 F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. Conclusion Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18 F-PI-2620 in patients along the AD trajectory. This work confirms that 18 F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders

“…A number of therapeutic trials have targeted amyloid pathology and slowing of accumulation [88] or reduction of aggregated amyloid levels below baseline values [89][90][91] provides evidence the disease biology is being modified by the therapeutic candidate. The recent advent of tau PET tracers [92][93][94][95][96][97][98][99], exhibiting a closer anatomical and temporal relationship to clinical symptoms than amyloid PET [100], has been an enabling feature for therapeutic programs targeting tau pathology and promises to provide another important window on how novel potential therapies interact with the Alzheimer's disease process in the living brain [101]. The development of PET tracers specific for protein aggregates underlying other neurological disorders will be similarly transformative for clinical drug development in those areas.…”

Case Report: [18F]PI2620 as a Tau Imaging Agent in Posterior Cortical Atrophy

“…In vitro and animal studies have shown that [ 18 F]PI2620 is highly selective for pathologic tau aggregates with no significant off-target binding to β-amyloid, MAO-A, or MAO-B and can be rapidly washed out from unaffected brain regions ( 5 , 14 ). In-human clinical studies confirmed that tracer uptake level generally corresponds to disease severity throughout the course of AD and can clearly distinguish AD patients from healthy controls ( 6 , 7 ). One study of four PCA cases showed robust increases in [ 18 F]PI2620 uptake throughout the posterior cortical regions with relative sparing of the medial frontal and temporal lobes, which was related to disease severity ( 6 ); this is the only study to date assessing tau burden in PCA by [ 18 F]PI2620 PET.…”

“…In-human clinical studies confirmed that tracer uptake level generally corresponds to disease severity throughout the course of AD and can clearly distinguish AD patients from healthy controls ( 6 , 7 ). One study of four PCA cases showed robust increases in [ 18 F]PI2620 uptake throughout the posterior cortical regions with relative sparing of the medial frontal and temporal lobes, which was related to disease severity ( 6 ); this is the only study to date assessing tau burden in PCA by [ 18 F]PI2620 PET. In accordance with previous studies, in our patient, [ 18 F]PI2620 uptake was more restricted to bilateral occipital cortices, consistent with the observed visuospatial and visuoperceptual deficits and brain atrophy and hypometabolism detected by MRI and [ 18 F]FDG PET, respectively.…”

“…[ 18 F]PI2620 is a next-generation tau-specific positron emission tomography (PET) tracer with high binding affinity for pathogenic tau protein but without off-target binding to β-amyloid, monoamine oxidase (MAO)-A, or MAO-B ( 5 ). Human studies have shown that [ 18 F]PI2620 can detect tau pathology throughout the course of AD ( 6 , 7 ). However, there have been few studies using [ 18 F]PI2620 PET in PCA, and its utility in this context has yet to be demonstrated.…”

Feasibility of Short Imaging Protocols for [18F]PI-2620 Tau-PET in Progressive Supranuclear Palsy

“…Here, we observed the most relevant drop of performance for 20-40 SUVr when compared to 0-60 DVR which is in line with the observation of increasing [ 18 F]PI-2620 SUVR over time in AD even beyond 60 minutes p.i. [29]. Thus, we recommend truncated dynamic imaging (0-40 DVR) when the mesial temporal lobe is subject of evaluation.…”