Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury

Abstract Purpose Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [18F]PI-2620 as a potential substitute for [18F]fluorodeoxyglucose ([18F]FDG). Methods Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson’s disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [18F]PI-2620 tau-PET (0–60 min p.i.) and static [18F]FDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R1) of [18F]PI-2620-PET were correlated with corresponding quantification of [18F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [18F]PI-2620 tau-PET and [18F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers. Results Highest agreement with [18F]FDG-PET quantification was reached for [18F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5–2.5 min SUVr & R1) displayed strong agreement in all cortical target regions for global mean (RSUVr 0.76, RR1 = 0.77) and cerebellar normalization (RSUVr 0.68, RR1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [18F]FDG-PET. There were no relevant differences between more and less experienced readers. Conclusion Early-phase imaging of [18F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [18F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.

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Perfusion-Phase 18 F-PI-2620 Tau-PET Imaging as a Surrogate Marker of Neuronal Injury

10.1055/s-0040-1708352 ◽

2020 ◽

Author(s):

L Beyer ◽

A Nitschmann ◽

H Barthel ◽

T van Eimeren ◽

M Unterrainer ◽

...

Keyword(s):

Pet Imaging ◽

Surrogate Marker ◽

Neuronal Injury ◽

Tau Pet ◽

Tau Pet Imaging

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Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?

Frontiers in Neurology ◽

10.3389/fneur.2018.00483 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Leonie Beyer ◽

Johanna Meyer-Wilmes ◽

Sonja Schönecker ◽

Jonas Schnabel ◽

Eva Brendel ◽

...

Keyword(s):

Progressive Supranuclear Palsy ◽

Pet Imaging ◽

Fdg Pet ◽

Corticobasal Degeneration ◽

Clinical Routine ◽

Tau Pet ◽

Tau Pet Imaging

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High Correlation of Static First-Minute-Frame (FMF) PET Imaging after 18F-Labeled Amyloid Tracer Injection with [18F]FDG PET Imaging

Sensors ◽

10.3390/s21155182 ◽

2021 ◽

Vol 21 (15) ◽

pp. 5182

Author(s):

Alexander P. Seiffert ◽

Adolfo Gómez-Grande ◽

Alberto Villarejo-Galende ◽

Marta González-Sánchez ◽

Héctor Bueno ◽

...

Keyword(s):

Pet Imaging ◽

Fdg Pet ◽

Early Phase ◽

Standardized Uptake Value ◽

Correlation Coefficients ◽

Dynamic Imaging ◽

Study Cohort ◽

Amyloid Pet ◽

Tracer Injection ◽

18F Fdg

Dynamic early-phase PET images acquired with radiotracers binding to fibrillar amyloid-beta (Aβ) have shown to correlate with [18F]fluorodeoxyglucose (FDG) PET images and provide perfusion-like information. Perfusion information of static PET scans acquired during the first minute after radiotracer injection (FMF, first-minute-frame) is compared to [18F]FDG PET images. FMFs of 60 patients acquired with [18F]florbetapir (FBP), [18F]flutemetamol (FMM), and [18F]florbetaben (FBB) are compared to [18F]FDG PET images. Regional standardized uptake value ratios (SUVR) are directly compared and intrapatient Pearson’s correlation coefficients are calculated to evaluate the correlation of FMFs to their corresponding [18F]FDG PET images. Additionally, regional interpatient correlations are calculated. The intensity profiles of mean SUVRs among the study cohort (r = 0.98, p < 0.001) and intrapatient analyses show strong correlations between FMFs and [18F]FDG PET images (r = 0.93 ± 0.05). Regional VOI-based analyses also result in high correlation coefficients. The FMF shows similar information to the cerebral metabolic patterns obtained by [18F]FDG PET imaging. Therefore, it could be an alternative to the dynamic imaging of early phase amyloid PET and be used as an additional neurodegeneration biomarker in amyloid PET studies in routine clinical practice while being acquired at the same time as amyloid PET images.

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Identifying degenerative effects of repetitive head trauma with neuroimaging: a clinically-oriented review

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01197-4 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Breton M. Asken ◽

Gil D. Rabinovici

Keyword(s):

Head Trauma ◽

Pet Imaging ◽

Fdg Pet ◽

Chronic Traumatic Encephalopathy ◽

Structural Mri ◽

Disease Diagnosis ◽

Underlying Disease ◽

American Football ◽

Cavum Septum Pellucidum ◽

Tau Pet

Abstract Background and Scope of Review Varying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aβ-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aβ-PET, and tau-PET in addition to comprehensive clinical examinations before death. Review Conclusions Group-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual’s head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer’s disease).

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