Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy

Abstract Purpose Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [18F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [18F]PI-2620 tau-PET imaging of PSP. Methods Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [18F]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0–60, 0–50, 0–40, 0–30, and 0–20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20–40, 30–50, and 40–60 min p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier). Results 0–50 and 0–40 DVR showed equivalent effect sizes as 0–60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0–30 or 0–20 DVR. The 20–40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0–60 DVR (AUC: 0.96), 0–40 DVR (AUC: 0.96), and 20–40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%. Conclusion Truncated and static imaging windows can be used for [18F]PI-2620 PET imaging of PSP. 0–40 min dynamic scanning offers the best balance between accuracy and economic scanning.

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

10.21203/rs.3.rs-180630/v1 ◽

2021 ◽

Author(s):

Mengmeng Song ◽

Maximilian Scheifele ◽

Henryk Barthel ◽

Thilo van Eimeren ◽

Leonie Beyer ◽

...

Keyword(s):

Progressive Supranuclear Palsy ◽

Pet Imaging ◽

Time Windows ◽

Area Under The Curve ◽

Standardized Uptake Value ◽

Cohen’S D ◽

Positron Emission ◽

Tau Pet ◽

High Level ◽

Cohen's D

Abstract PurposeDynamic 60-minute positron-emission-tomography (PET) imaging with the novel tau radiotracer [18F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [18F]PI-2620 tau-PET imaging of PSP. MethodsThirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [18F]PI-2620 PET was performed by a dynamic 60 minute scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0-60, 0-50, 0-40, 0-30, and 0-20 minutes p.i.). Standardized uptake value ratios (SUVrs) were obtained 20-40, 30-50, and 40-60 minutes p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier).Results0-50 and 0-40 DVR showed equivalent effect sizes as 0-60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0-30 or 0-20 DVR. The 20-40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0-60 DVR (AUC: 0.96), 0-40 DVR (AUC: 0.96), and 20-40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%.ConclusionTruncated and static imaging windows can be used for [18F]PI-2620 PET imaging of PSP. 0-40 minute dynamic scanning offers the best balance between accuracy and economic scanning.

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Medial temporal tau can be a predictor for amyloid-ß positivity in mild cognitive impairment

10.21203/rs.3.rs-16213/v1 ◽

2020 ◽

Author(s):

Hanna Cho ◽

Min Seok Baek ◽

Hye Sun Lee ◽

Jae Yong Choi ◽

Jae Hoon Lee ◽

...

Keyword(s):

Area Under The Curve ◽

Standardized Uptake Value ◽

Visual Assessment ◽

Parahippocampal Cortex ◽

Positron Emission ◽

Auc Value ◽

Tau Pet ◽

Sensitivity Specificity ◽

Post Hoc ◽

Pet Scans

Abstract Introduction Although both amyloid-ß (Aß) and tau positron emission tomography (PET) are important for the assessment of Alzheimer’s disease pathology, obtaining two PET scans can be challenging in clinical practice. We sought to determine whether Aß-positivity in MCI patients can be predicted with only a single tau PET scan. Methods We prospectively recruited 105 MCI patients and performed two PET scans with 18 F-florbetaben and 18 F-flortaucipir with all patients. Regional 18 F-flortaucipir standardized uptake value ratios (SUVR) were measured using FreeSurfer-generated volumes-of-interest and with the cerebellar crus median as a reference. Results We classified 49 (46.7%) MCI patients as Aß-positive using visual assessment. In 12 regions showing greater tau uptake in the MCI-Aβ+ patients compared to the MCI-Aβ- patients, tau uptake in the entorhinal cortex showed the greatest area under the curve (AUC) value (AUC = 0.835, sensitivity/specificity = 73.5% /85.7%) for discriminating Aß-positivity. The second and third largest AUCs were obtained with tau uptake in the amygdala (AUC = 0.814, sensitivity/specificity = 65.3%/94.6%) and the parahippocampal cortex (AUC = 0.802, sensitivity/specificity = 67.4%/91.1%). However, post-hoc analyses revealed no statistical differences between the three regions. Conclusions Single tau PET scans may be helpful in the evaluation of disease state and stage at the same time in MCI patients.

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Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system

Journal of Neurosurgery ◽

10.3171/2019.5.jns19780 ◽

2020 ◽

Vol 133 (4) ◽

pp. 1010-1019 ◽

Cited By ~ 4

Author(s):

Hiroaki Takei ◽

Jun Shinoda ◽

Soko Ikuta ◽

Takashi Maruyama ◽

Yoshihiro Muragaki ◽

...

Keyword(s):

Positron Emission Tomography ◽

Pet Imaging ◽

Who Classification ◽

Standardized Uptake Value ◽

Emission Tomography ◽

World Health ◽

Pet Tracers ◽

Positron Emission ◽

Significant Difference ◽

The Mean

OBJECTIVEPositron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification.METHODSIn total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers.RESULTSThere were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG.CONCLUSIONSPET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

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Texture-Based Analysis of 18F-Labeled Amyloid PET Brain Images

Applied Sciences ◽

10.3390/app11051991 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1991

Author(s):

Alexander P. Seiffert ◽

Adolfo Gómez-Grande ◽

Eva Milara ◽

Sara Llamas-Velasco ◽

Alberto Villarejo-Galende ◽

...

Keyword(s):

Area Under The Curve ◽

Standardized Uptake Value ◽

Texture Features ◽

Roc Curves ◽

Significant Feature ◽

Study Cohort ◽

Amyloid Pet ◽

Reference Region ◽

Brain Images ◽

Positron Emission

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [18F]florbetapir (FBP) or [18F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, the reference region could present high variability in longitudinal studies. Texture features based on the grey-level co-occurrence matrix, also called Haralick features (HF), are evaluated in this study to discriminate between amyloid-positive and negative cases. A retrospective study cohort of 66 patients with amyloid PET images (30 [18F]FBP and 36 [18F]FMM) was selected and SUVRs and 6 HFs were extracted from 13 cortical volumes of interest. Mann–Whitney U-tests were performed to analyze differences of the features between amyloid positive and negative cases. Receiver operating characteristic (ROC) curves were computed and their area under the curve (AUC) was calculated to study the discriminatory capability of the features. SUVR proved to be the most significant feature among all tests with AUCs between 0.692 and 0.989. All HFs except correlation also showed good performance. AUCs of up to 0.949 were obtained with the HFs. These results suggest the potential use of texture features for the classification of amyloid PET images.

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Prognostic value of positron emission tomography and preoperative CA19-9 in patients treated on a prospective phase II trial of neoadjuvant therapy and surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15766 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15766-e15766

Author(s):

Chad Barnes ◽

Mohammed Aldakkak ◽

Kathleen K. Christians ◽

Parag Tolat ◽

Paul S. Ritch ◽

...

Keyword(s):

Positron Emission Tomography ◽

Neoadjuvant Therapy ◽

Pet Imaging ◽

Fdg Pet ◽

Prognostic Value ◽

Prospective Trial ◽

Standardized Uptake Value ◽

Carbohydrate Antigen ◽

Emission Tomography ◽

Positron Emission

e15766 Background: The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging of pancreatic cancer (PC) has not been well defined. We evaluated the prognostic value of FDG-PET imaging in patients with localized PC enrolled in a prospective trial of personalized molecular-directed neoadjuvant therapy. Methods: Pretreatment FDG-PET was classified as high or low based on a standardized uptake value (SUV) cutpoint of 7.2 (population median). Carbohydrate antigen 19-9 (CA19-9) was measured after the completion of neoadjuvant therapy (preoperative) and classified as normal (≤35 U/mL) or elevated. Results: Pretreatment FDG-PET imaging was performed on 100 consecutive patients; SUV was high in 50 and low in 50. Preoperative CA19-9 values were available in 99 of 100 patients; 54 (55%) were elevated and 45 (45%) were normal. Of the 100 patients, 81 completed neoadjuvant therapy and surgery, and 19 were not resected. Among the 81 resected patients, SUV was high in 37 (46%) and low in 44 (54%); preoperative CA19-9 was elevated in 40 (49%) and normal in 41 (51%). The median overall survival (OS) for all patients was 39 months; 45 months for who completed all intended neoadjuvant therapy and surgery and 9 months for patients who were not resected. The median OS for patients with normal CA19-9/low SUV, normal CA19-9/high SUV, elevated CA19-9/low SUV, and elevated CA19-9/high SUV were not reached, 35, 24, and 18 months, respectively (p = 0.0001). Conclusions: Pretreatment FDG-PET avidity and preoperative CA19-9 are important prognostic markers and may be used to estimate the anticipated benefit of surgery; information of immediate clinical significance for both treatment sequencing and the application of surgery to patients who are frequently of advanced age or high-risk.

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Association of Surgical Hospitalization with Brain Amyloid Deposition

Anesthesiology ◽

10.1097/aln.0000000000003255 ◽

2020 ◽

Vol 132 (6) ◽

pp. 1407-1418 ◽

Cited By ~ 1

Author(s):

Keenan A. Walker ◽

Rebecca F. Gottesman ◽

Josef Coresh ◽

A. Richey Sharrett ◽

David S. Knopman ◽

...

Keyword(s):

Older Adults ◽

Pet Imaging ◽

Odds Ratio ◽

Reference Group ◽

Secondary Analysis ◽

Standardized Uptake Value ◽

Amyloid Deposition ◽

Long Term Effects ◽

Primary Analysis ◽

Positron Emission

Abstract Background As more older adults undergo surgery, it is critical to understand the long-term effects of surgery on brain health, particularly in relation to the development of Alzheimer’s disease. This study examined the association of surgical hospitalization with subsequent brain β-amyloid deposition in nondemented older adults. Methods The Atherosclerosis Risk in Communities–Positron Emission Tomography (ARIC–PET) study is a prospective cohort study of 346 participants without dementia who underwent florbetapir PET imaging. Active surveillance of local hospitals and annual participant contact were used to gather hospitalization and surgical information (International Classification of Disease, Ninth Revision, Clinical Modification codes) over the preceding 24-yr period. Brain amyloid measured using florbetapir PET imaging was the primary outcome. Elevated amyloid was defined as a standardized uptake value ratio of more than 1.2. Results Of the 313 participants included in this analysis (age at PET: 76.0 [SD 5.4]; 56% female), 72% had a prior hospitalization, and 50% had a prior surgical hospitalization. Elevated amyloid occurred in 87 of 156 (56%) participants with previous surgical hospitalization, compared with 45 of 87 (52%) participants who had no previous hospitalization. Participants with previous surgical hospitalizations did not show an increased odds of elevated brain amyloid (odds ratio, 1.32; 95% CI, 0.72 to 2.40; P = 0.370) after adjusting for confounders (primary analysis). Results were similar using the reference group of all participants without previous surgery (hospitalized and nonhospitalized; odds ratio, 1.58; 95% CI, 0.96 to 2.58; P = 0.070). In a prespecified secondary analysis, participants with previous surgical hospitalization did demonstrate increased odds of elevated amyloid when compared with participants hospitalized without surgery (odds ratio, 2.10; 95% CI, 1.09 to 4.05; P = 0.026). However, these results were attenuated and nonsignificant when alternative thresholds for amyloid-positive status were used. Conclusions The results do not support an association between surgical hospitalization and elevated brain amyloid. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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M7. LOWER THALAMIC DOPAMINE D2-RECEPTOR BINDING IN DRUG-NAIVE PATIENTS WITH PSYCHOSIS – A REPLICATION STUDY USING POSITRON EMISSION TOMOGRAPHY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.319 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S135-S136

Author(s):

Pauliina Victorsson ◽

Pontus Plavén-Sigray ◽

Granville Matheson ◽

Alexander Santillo ◽

Maria Lee ◽

...

Keyword(s):

High Resolution ◽

Bayes Factor ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

First Episode Psychosis ◽

First Episode ◽

Cohen’S D ◽

Positron Emission ◽

Episode Psychosis ◽

Cohen's D

Abstract Background The dopamine system is a central focus of research on the pathophysiology and treatment of schizophrenia. With regard to the dopamine D2-receptor (D2-R), Positron Emission Tomography (PET) studies have shown a small increase in striatal receptor availability. In contrast, a more recent line of research has demonstrated lower levels of D2-R (Cohen’s D = -0.32) in the thalamus, a region of key interest for the pathophysiology of schizophrenia. However, some studies included patients previously on antipsychotic medication, or were performed using radioligands with suboptimal affinity for the much lower D2-R density in thalamus compared to striatum. In addition, the resolution of previous PET systems has not allowed for a more detailed analysis of functional thalamic subregions. Here we examined a fully antipsychotic-naïve sample of first-episode psychosis patients using the high-affinity D2-R radioligand [11C]FLB457 and high-resolution PET. The aim was to a) replicate previous findings of lower D2-R in thalamus in patients and b) specifically examine patient-control differences in thalamic subregions based on their cortical connectivity. Methods Nineteen antipsychotic-naïve first episode psychosis patients (mean age = 29.3; sd = 6.3, 11 males) and 19 age- and sex matched healthy comparison subjects were included in the analysis. PET measurements were obtained using a High Resolution Research Tomograph (HRRT). A ROI for whole thalamus was defined using the FSL Harvard Oxford Subcortical Atlas, whereas ROIs for thalamic subregions were based on the Oxford Thalamic Connectivity Atlas. Binding potential (BPND) was calculated using the Logan graphical analysis with cerebellum as reference region. The statistical analyses, which were all pre-registered, were performed using frequentist and Bayesian paired-samples t-tests. Results The frequentist paired t-test showed that patients had significantly lower binding than control subjects in whole thalamus (Cohen’s D = -0.479, p = 0.026). Bayes factor from the Bayesian paired t-test indicated that there was approximately 5 times more support for the hypothesis of lower BPND in patients, compared to the null hypothesis of no difference. Among subregions, the ROI corresponding to prefrontal thalamic connectivity showed the largest effect (Cohen’s D = -0.527, p = 0.017), and Bayes factor indicated that there was 6 times more support for lower BPND in patients compared to no difference. Discussion Using high resolution PET and a high affinity D2-R radioligand in antipsychotic-naïve first-episode psychosis patients, this study replicates the previously reported meta-analytical effect size of lower thalamic receptor availability in patients. The strongest effect was observed in the subregion dominated by connections to prefrontal cortex. The findings may reflect a dysregulation of the thalamic dopamine system in schizophrenia, which in turn could underlie aberrant functional connectivity in key fronto-thalamic circuits.

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Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

Pharmaceuticals ◽

10.3390/ph14020110 ◽

2021 ◽

Vol 14 (2) ◽

pp. 110

Author(s):

Caitlin Jie ◽

Valerie Treyer ◽

Roger Schibli ◽

Linjing Mu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pet Imaging ◽

Second Generation ◽

Tau Proteins ◽

Tau Pathology ◽

Pet Tracer ◽

Positron Emission ◽

Tau Pet ◽

Target Binding

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

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Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies

Brain Communications ◽

10.1093/braincomms/fcab190 ◽

2021 ◽

Vol 3 (4) ◽

Cited By ~ 1

Author(s):

Toshiki Tezuka ◽

Keisuke Takahata ◽

Morinobu Seki ◽

Hajime Tabuchi ◽

Yuki Momota ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Progressive Supranuclear Palsy ◽

Standardized Uptake Value ◽

Corticobasal Degeneration ◽

Post Injection ◽

Healthy Controls ◽

Tau Pathology ◽

Tau Pet

Abstract Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisition at 60–90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.

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