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101. Improved Imaging-Based Diagnosis of PSP by [F-18]PI-2620 Tau PET

Author

Messerschmidt, Konstantin, Barthel, Henryk, Brendel, Matthias, Van Eimeren, Thilo, Marek, Kenneth, Villemagne, Victor, Rumpf, Jost-Julian, Saur, Dorothee, Schroeter, Matthias, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Beyer, Leonie, Song, Mengmeng, Palleis, Carla, Gehmeyr, Mona, Fietzek, Urban, Hammes, Jochen, Stephens, Andrew, Bartenstein, Peter, Drzezga, Alexander, Seibyl, John, Hoeglinger, Guenter, Classen, Joseph, Sabri, Osama, Messerschmidt, Konstantin, Barthel, Henryk, Brendel, Matthias, Van Eimeren, Thilo, Marek, Kenneth, Villemagne, Victor, Rumpf, Jost-Julian, Saur, Dorothee, Schroeter, Matthias, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Beyer, Leonie, Song, Mengmeng, Palleis, Carla, Gehmeyr, Mona, Fietzek, Urban, Hammes, Jochen, Stephens, Andrew, Bartenstein, Peter, Drzezga, Alexander, Seibyl, John, Hoeglinger, Guenter, Classen, Joseph, and Sabri, Osama

Published
2020

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

Author

Beyer, Leonie, Nitschmann, Alexander, Barthel, Henryk, van Eimeren, Thilo, Unterrainer, Marcus, Sauerbeck, Julia, Marek, Ken, Song, Mengmeng, Palleis, Carla, Respondek, Gesine, Hammes, Jochen, Barbe, Michael T., Onur, Oezguer, Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Neumaier, Bernd, Barret, Olivier, Madonia, Jennifer, Russell, David S., Stephens, Andrew W., Roeber, Sigrun, Herms, Jochen, Boetzel, Kai, Levin, Johannes, Classen, Joseph, Hoeglinger, Guenter U., Bartenstein, Peter, Villemagne, Victor, Drzezga, Alexander, Seibyl, John, Sabri, Osama, Brendel, Matthias, Beyer, Leonie, Nitschmann, Alexander, Barthel, Henryk, van Eimeren, Thilo, Unterrainer, Marcus, Sauerbeck, Julia, Marek, Ken, Song, Mengmeng, Palleis, Carla, Respondek, Gesine, Hammes, Jochen, Barbe, Michael T., Onur, Oezguer, Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Neumaier, Bernd, Barret, Olivier, Madonia, Jennifer, Russell, David S., Stephens, Andrew W., Roeber, Sigrun, Herms, Jochen, Boetzel, Kai, Levin, Johannes, Classen, Joseph, Hoeglinger, Guenter U., Bartenstein, Peter, Villemagne, Victor, Drzezga, Alexander, Seibyl, John, Sabri, Osama, and Brendel, Matthias

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 beta-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 [F-18]PI-2620 as a potential substitute for [F-18]fluorodeoxyglucose ([F-18]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 [F-18]PI-2620 tau-PET (0-60 min p.i.) and static [F-18]FDG-PET (30-50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R-1) of [F-18]PI-2620-PET were correlated with corresponding quantification of [F-18]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 [F-18]PI-2620 tau-PET and [F-18]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 [F-18]FDG-PET quantification was reached for [F-18]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 & R-1) displayed strong agreement in all cortical target regions for global mean (R-SUVr 0.76, R-R1 = 0.77) and cerebellar normalization (R-SUVr 0.68, R-R1 = 0.68). Visual i

Published
2020

103. Assessment of F-18-PI-2620 as a Biomarker in Progressive Supranuclear Palsy

Author

Brendel, Matthias, Barthel, Henryk, van Eimeren, Thilo, Marek, Ken, Beyer, Leonie, Song, Mengmeng, Palleis, Carla, Gehmeyr, Mona, Fietzek, Urban, Respondek, Gesine, Sauerbeck, Julia, Nitschmann, Alexander, Zach, Christian, Hammes, Jochen, Barbe, Michael T., Onur, Oezguer, Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Neumaier, Bernd, Barret, Olivier, Madonia, Jennifer, Russell, David S., Stephens, Andrew, Roeber, Sigrun, Herms, Jochen, Boetzel, Kai, Classen, Joseph, Bartenstein, Peter, Villemagne, Victor, Levin, Johannes, Hoeglinger, Guenter U., Drzezga, Alexander, Seibyl, John, Sabri, Osama, Brendel, Matthias, Barthel, Henryk, van Eimeren, Thilo, Marek, Ken, Beyer, Leonie, Song, Mengmeng, Palleis, Carla, Gehmeyr, Mona, Fietzek, Urban, Respondek, Gesine, Sauerbeck, Julia, Nitschmann, Alexander, Zach, Christian, Hammes, Jochen, Barbe, Michael T., Onur, Oezguer, Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Neumaier, Bernd, Barret, Olivier, Madonia, Jennifer, Russell, David S., Stephens, Andrew, Roeber, Sigrun, Herms, Jochen, Boetzel, Kai, Classen, Joseph, Bartenstein, Peter, Villemagne, Victor, Levin, Johannes, Hoeglinger, Guenter U., Drzezga, Alexander, Seibyl, John, and Sabri, Osama

Abstract

Importance Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective To investigate the potential of the novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants In this cross-sectional study, participants underwent dynamic F-18-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, F-18-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [

Published
2020

104. Training the next generation of radiopharmaceutical scientists

Author

Gee, Antony D., Andersson, Jan, Bhalla, Rajiv, Choe, Yearn Seong, Dick, David W., Herth, Matthias M., Hostetler, Eric D., Jauregui-Haza, Ulises J., Huang, Ya-Yao, James, Michelle L., Jeong, Jae Min, Korde, Aruna, Kuge, Yuji, Kung, Hank F., Lapi, Suzanne E., Osso, Joao Alberto, Parent, Ephraim, Patt, Marianne, Pricile, Ekoume Fany, Riss, Patrick J., Santos-Oliveira, Ralph, Taylor, Stephen, Vasdev, Neil, Vercouillie, Johnny, Wadsak, Wolfgang, Yang, Zhi, Zhu, Hua, Scott, Peter J. H., Gee, Antony D., Andersson, Jan, Bhalla, Rajiv, Choe, Yearn Seong, Dick, David W., Herth, Matthias M., Hostetler, Eric D., Jauregui-Haza, Ulises J., Huang, Ya-Yao, James, Michelle L., Jeong, Jae Min, Korde, Aruna, Kuge, Yuji, Kung, Hank F., Lapi, Suzanne E., Osso, Joao Alberto, Parent, Ephraim, Patt, Marianne, Pricile, Ekoume Fany, Riss, Patrick J., Santos-Oliveira, Ralph, Taylor, Stephen, Vasdev, Neil, Vercouillie, Johnny, Wadsak, Wolfgang, Yang, Zhi, Zhu, Hua, and Scott, Peter J. H.

Published
2020

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

Author

Song, Mengmeng, primary, Scheifele, Maximilian, additional, Barthel, Henryk, additional, Eimeren, Thilo van, additional, Beyer, Leonie, additional, Marek, Ken, additional, Eckenweber, Florian, additional, Palleis, Carla, additional, Kaiser, Lena, additional, Finze, Anika, additional, Kern, Maike, additional, Nitschmann, Alexander, additional, Biechele, Gloria, additional, Katzdobler, Sabrina, additional, Bischof, Gerard, additional, Hammes, Jochen, additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias, additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Stephens, Andrew, additional, Rauchmann, Boris, additional, Perneczky, Robert, additional, Levin, Johannes, additional, Classen, Joseph, additional, Neumeier, Bernd, additional, Höglinger, Günter, additional, Bartenstein, Peter, additional, Boening, Guido, additional, Ziegler, Sibylle, additional, Villemagne, Victor, additional, Drzezga, Alexander, additional, Seibyl, John, additional, Sabri, Osama, additional, and Brendel, Matthias, additional

Published
2021
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107. 18 F‐PI‐2620 tau‐PET in corticobasal syndrome (ActiGliA cohort)

Author

Brendel, Matthias, primary, Palleis, Carla, additional, Prix, Catharina, additional, Finze, Anika, additional, Boetzel, Kai, additional, Danek, Adrian, additional, Höllerhage, Matthias, additional, Beyer, Leonie, additional, Sauerbeck, Julia, additional, Rauchmann, Boris, additional, Stephens, Andrew W, additional, Drzezga, Alexander, additional, van Eimeren, Thilo, additional, Barthel, Henryk, additional, Patt, Marianne, additional, Sabri, Osama, additional, Villemagne, Victor LL, additional, Bartenstein, Peter, additional, Perneczky, Robert, additional, Haass, Christian, additional, Levin, Johannes, additional, and Höglinger, Günter, additional

Published
2020
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108. Multicenter 18 F-PI-2620 PET for In Vivo Braak Staging of Tau Pathology in Alzheimer's Disease.

Author

Rullmann, Michael, Brendel, Matthias, Schroeter, Matthias L., Saur, Dorothee, Levin, Johannes, Perneczky, Robert G., Tiepolt, Solveig, Patt, Marianne, Mueller, Andre, Villemagne, Victor L., Classen, Joseph, Stephens, Andrew W., Sabri, Osama, and Barthel, Henryk

Subjects
TAU proteins, ALZHEIMER'S disease, DEMENTIA patients
Abstract

Tau aggregates accumulate in the Alzheimer's disease (AD) brain according to the established Braak staging scheme and spread from transentorhinal over limbic regions to the neocortex. To impact the management of AD patients, an in vivo tool for tau Braak staging is needed. First-generation tau tracers have limited performance in detecting early stages of tau. Therefore, we tested the corresponding capability of the next-generation tau tracer, 18F-PI-2620. We analyzed 18F-PI-2620 multicenter PET data from 37 beta-amyloid-positive AD dementia patients and those from 26 healthy controls. We applied kinetic modeling of the 0–60 min p.i. PET data using MRTM2 with the lower cerebellum as the reference region to extract Braak stage-dependent distribution volume ratios, whereas controls were used to define Braak stage PET positivity thresholds. Stage-dependent PET positivity widely followed the Braak scheme (except Braak stage III) presenting descending frequency of PET positivity from Braak I (43%), II (38%), III (49%), IV (35%), V (30%) to VI (14%). A strictly hierarchical model was met by 64% of AD dementia cases. Nineteen percent showed a hippocampal sparing tauopathy pattern. Thus, we could assign 87% to the six-stage hierarchical Braak model including tauopathy variants. 18F-PI-2620 PET appears to be able to perform Braak tau staging of AD in vivo. [ABSTRACT FROM AUTHOR]

Published
2022
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110. Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy

Author

Brendel, Matthias, primary, Barthel, Henryk, additional, van Eimeren, Thilo, additional, Marek, Ken, additional, Beyer, Leonie, additional, Song, Mengmeng, additional, Palleis, Carla, additional, Gehmeyr, Mona, additional, Fietzek, Urban, additional, Respondek, Gesine, additional, Sauerbeck, Julia, additional, Nitschmann, Alexander, additional, Zach, Christian, additional, Hammes, Jochen, additional, Barbe, Michael T., additional, Onur, Oezguer, additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias L., additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Neumaier, Bernd, additional, Barret, Olivier, additional, Madonia, Jennifer, additional, Russell, David S., additional, Stephens, Andrew, additional, Roeber, Sigrun, additional, Herms, Jochen, additional, Bötzel, Kai, additional, Classen, Joseph, additional, Bartenstein, Peter, additional, Villemagne, Victor, additional, Levin, Johannes, additional, Höglinger, Günter U., additional, Drzezga, Alexander, additional, Seibyl, John, additional, and Sabri, Osama, additional

Published
2020
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113. Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [18F] fluspidine and [18F] fallypride PET study

Author

Grachev, Igor D., primary, Meyer, Philipp M., additional, Becker, Georg A., additional, Bronzel, Marcus, additional, Marsteller, Doug, additional, Pastino, Gina, additional, Voges, Ole, additional, Rabinovich, Laura, additional, Knebel, Helena, additional, Zientek, Franziska, additional, Rullmann, Michael, additional, Sattler, Bernhard, additional, Patt, Marianne, additional, Gerhards, Thilo, additional, Strauss, Maria, additional, Kluge, Andreas, additional, Brust, Peter, additional, Savola, Juha-Matti, additional, Gordon, Mark F., additional, Geva, Michal, additional, Hesse, Swen, additional, Barthel, Henryk, additional, Hayden, Michael R., additional, and Sabri, Osama, additional

Published
2020
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114. (+)-[18F]Flubatine as a novel α4β2 nicotinic acetylcholine receptor PET ligand—results of the first-in-human brain imaging application in patients with β-amyloid PET-confirmed Alzheimer’s disease and healthy controls

Author

Tiepolt, Solveig, primary, Becker, Georg-Alexander, additional, Wilke, Stephan, additional, Cecchin, Diego, additional, Rullmann, Michael, additional, Meyer, Philipp M., additional, Barthel, Henryk, additional, Hesse, Swen, additional, Patt, Marianne, additional, Luthardt, Julia, additional, Wagenknecht, Gudrun, additional, Sattler, Bernhard, additional, Deuther-Conrad, Winnie, additional, Ludwig, Friedrich-Alexander, additional, Fischer, Steffen, additional, Gertz, Hermann-Josef, additional, Smits, René, additional, Hoepping, Alexander, additional, Steinbach, Jörg, additional, Brust, Peter, additional, and Sabri, Osama, additional

Published
2020
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116. Training the next generation of radiopharmaceutical scientists

Author

Gee, Antony D., primary, Andersson, Jan, additional, Bhalla, Rajiv, additional, Choe, Yearn Seong, additional, Dick, David W., additional, Herth, Matthias M., additional, Hostetler, Eric D., additional, Jáuregui-Haza, Ulises J., additional, Huang, Ya-Yao, additional, James, Michelle L., additional, Jeong, Jae Min, additional, Korde, Aruna, additional, Kuge, Yuji, additional, Kung, Hank F., additional, Lapi, Suzanne E., additional, Osso, Joao Alberto, additional, Parent, Ephraim, additional, Patt, Marianne, additional, Pricile, Ekoume Fany, additional, Riss, Patrick J., additional, Santos-Oliveira, Ralph, additional, Taylor, Stephen, additional, Vasdev, Neil, additional, Vercouillie, Johnny, additional, Wadsak, Wolfgang, additional, Yang, Zhi, additional, Zhu, Hua, additional, and Scott, Peter J.H., additional

Published
2020
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118. Colocalization of Tau but Not β-Amyloid with Cortical Superficial Siderosis in a Case with Probable CAA

Author

Brendel, Matthias, primary, Catak, Cihan, additional, Beyer, Leonie, additional, Linn, Jennifer, additional, Wahl, Hannes, additional, Janowitz, Daniel, additional, Rominger, Axel, additional, Patt, Marianne, additional, Barthel, Henryk, additional, Sabri, Osama, additional, Bartenstein, Peter, additional, and Wollenweber, Frank Arne, additional

Published
2020
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121. Cortical [18F]PI‐2620 Binding Differentiates Corticobasal Syndrome Subtypes.

Author

Palleis, Carla, Brendel, Matthias, Finze, Anika, Weidinger, Endy, Bötzel, Kai, Danek, Adrian, Beyer, Leonie, Nitschmann, Alexander, Kern, Maike, Biechele, Gloria, Rauchmann, Boris‐Stephan, Häckert, Jan, Höllerhage, Matthias, Stephens, Andrew W., Drzezga, Alexander, van Eimeren, Thilo, Villemagne, Victor L., Schildan, Andreas, Barthel, Henryk, and Patt, Marianne

Abstract

Background: Corticobasal syndrome is associated with cerebral protein aggregates composed of 4‐repeat (~50% of cases) or mixed 3‐repeat/4‐repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases). Objectives: The aim of this single‐center study was to investigate the diagnostic value of the tau PET‐ligand [18F]PI‐2620 in patients with corticobasal syndrome. Methods: Forty‐five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age‐matched healthy controls underwent [18F]PI‐2620‐PET. Beta‐amyloid status was determined by cerebral β‐amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI‐2620 binding was quantitatively and visually compared between β‐amyloid‐positive and ‐negative patients and controls. Regional [18F]PI‐2620 binding was correlated with clinical and demographic data. Results: Twenty‐four percent (11 of 45) were β‐amyloid‐positive. Significantly elevated [18F]PI‐2620 distribution volume ratios were observed in both β‐amyloid‐positive and β‐amyloid‐negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI‐2620 PET positivity was distinctly higher in β‐amyloid‐positive compared with β‐amyloid‐negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI‐2620 PET revealed a sensitivity of 91% for β‐amyloid‐positive and of 65% for β‐amyloid‐negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β‐amyloid status, hemispheric lateralization of [18F]PI‐2620 signal reflected contralateral predominance of clinical disease severity. Conclusions: Our data indicate a value of [18F]PI‐2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β‐amyloid‐positive as well as β‐amyloid‐negative corticobasal syndrome. In corticobasal syndrome, [18F]PI‐2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2021
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124. Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [ 18 F]PI-2620.

Author

Willroider, Marie, Roeber, Sigrun, Horn, Anja K. E., Arzberger, Thomas, Scheifele, Maximilian, Respondek, Gesine, Sabri, Osama, Barthel, Henryk, Patt, Marianne, Mishchenko, Olena, Schildan, Andreas, Mueller, André, Koglin, Norman, Stephens, Andrew, Levin, Johannes, Höglinger, Günter U., Bartenstein, Peter, Herms, Jochen, Brendel, Matthias, and Beyer, Leonie

Subjects
PROGRESSIVE supranuclear palsy, TAU proteins, POSITRON emission tomography, ALZHEIMER'S patients, AUTORADIOGRAPHY
Abstract

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.). Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients. [ABSTRACT FROM AUTHOR]

Published
2021
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125. P2-376: 18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION

Author

Brendel, Matthias, primary, Barthel, Henryk, additional, van Eimeren, Thilo, additional, Marek, Ken, additional, Beyer, Leonie, additional, Song, Mengmeng, additional, Palleis, Carla, additional, Respondek, Gesine, additional, Sauerbeck, Julia, additional, Hammes, Jochen, additional, Barbe, Michael, additional, Onur, Oezguer A., additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias L., additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Barret, Oliver, additional, Madonia, Jennifer, additional, Russell, David, additional, Stephens, Andrew Wills, additional, Roeber, Sigrun, additional, Herms, Jochen, additional, Boetzel, Kai, additional, Levin, Johannes, additional, Classen, Joseph, additional, Höglinger, Günter, additional, Bartenstein, Peter, additional, Drzezga, Alexander, additional, Seibyl, John, additional, and Sabri, Osama, additional

Published
2019
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126. IC‐P‐161: 18F‐PI2620 TAU‐PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI‐CENTER EVALUATION

Author

Brendel, Matthias, primary, Barthel, Henryk, additional, van Eimeren, Thilo, additional, Marek, Ken, additional, Beyer, Leonie, additional, Song, Mengmeng, additional, Palleis, Carla, additional, Respondek, Gesine, additional, Sauerbeck, Julia, additional, Hammes, Jochen, additional, Barbe, Michael, additional, Onur, Oezguer A., additional, Jessen, Frank, additional, Saur, Dorothee, additional, Schroeter, Matthias L., additional, Rumpf, Jost-Julian, additional, Rullmann, Michael, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Barret, Oliver, additional, Madonia, Jennifer, additional, Russell, David, additional, Stephens, Andrew Wills, additional, Roeber, Sigrun, additional, Herms, Jochen, additional, Boetzel, Kai, additional, Levin, Johannes, additional, Classen, Joseph, additional, Höglinger, Günter, additional, Bartenstein, Peter, additional, Drzezga, Alexander, additional, Seibyl, John, additional, and Sabri, Osama, additional

Published
2019
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127. In vitro and in vivo Human Metabolism of (S)-[18F]Fluspidine – A Radioligand for Imaging σ1 Receptors With Positron Emission Tomography (PET)

Author

Ludwig, Friedrich-Alexander, primary, Fischer, Steffen, additional, Houska, Richard, additional, Hoepping, Alexander, additional, Deuther-Conrad, Winnie, additional, Schepmann, Dirk, additional, Patt, Marianne, additional, Meyer, Philipp M., additional, Hesse, Swen, additional, Becker, Georg-Alexander, additional, Zientek, Franziska Ruth, additional, Steinbach, Jörg, additional, Wünsch, Bernhard, additional, Sabri, Osama, additional, and Brust, Peter, additional

Published
2019
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134. Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury.

Author

Beyer, Leonie, Nitschmann, Alexander, Barthel, Henryk, van Eimeren, Thilo, Unterrainer, Marcus, Sauerbeck, Julia, Marek, Ken, Song, Mengmeng, Palleis, Carla, Respondek, Gesine, Hammes, Jochen, Barbe, Michael T., Onur, Özgür, Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, and Patt, Marianne

Subjects
BIOMARKERS, POSITRON emission tomography, PROGRESSIVE supranuclear palsy, RANK correlation (Statistics), PARKINSON'S disease, PARKINSONIAN disorders, OCHRATOXINS
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. [ABSTRACT FROM AUTHOR]

Published
2020
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135. Dual Time-Point [18F]Florbetaben PET Delivers Dual Biomarker Information in Mild Cognitive Impairment and Alzheimer’s Disease

Author

Florek, Lisa, primary, Tiepolt, Solveig, additional, Schroeter, Matthias L., additional, Berrouschot, Jörg, additional, Saur, Dorothee, additional, Hesse, Swen, additional, Jochimsen, Thies, additional, Luthardt, Julia, additional, Sattler, Bernhard, additional, Patt, Marianne, additional, Hoffmann, Karl-Titus, additional, Villringer, Arno, additional, Classen, Joseph, additional, Gertz, Hermann-Josef, additional, Sabri, Osama, additional, and Barthel, Henryk, additional

Published
2018
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136. Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls

Author

Schinke, Christian, primary, Hesse, Swen, additional, Rullmann, Michael, additional, Becker, Georg-Alexander, additional, Luthardt, Julia, additional, Zientek, Franziska, additional, Patt, Marianne, additional, Stoppe, Muriel, additional, Schmidt, Elisa, additional, Meyer, Klara, additional, Meyer, Philipp M., additional, Orthgieß, Johannes, additional, Blüher, Matthias, additional, Kratzsch, Jürgen, additional, Ding, Yu-Shin, additional, Then Bergh, Florian, additional, and Sabri, Osama, additional

Published
2018
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137. Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer’s dementia

Author

Sabri, Osama, primary, Meyer, Philipp M, additional, Gräf, Susanne, additional, Hesse, Swen, additional, Wilke, Stephan, additional, Becker, Georg-Alexander, additional, Rullmann, Michael, additional, Patt, Marianne, additional, Luthardt, Julia, additional, Wagenknecht, Gudrun, additional, Hoepping, Alexander, additional, Smits, Rene, additional, Franke, Annegret, additional, Sattler, Bernhard, additional, Tiepolt, Solveig, additional, Fischer, Steffen, additional, Deuther-Conrad, Winnie, additional, Hegerl, Ulrich, additional, Barthel, Henryk, additional, Schönknecht, Peter, additional, and Brust, Peter, additional

Published
2018
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139. The association between in vivo central noradrenaline transporter availability and trait impulsivity

Author

Hesse, Swen, primary, Müller, Ulrich, additional, Rullmann, Michael, additional, Luthardt, Julia, additional, Bresch, Anke, additional, Becker, Georg-Alexander, additional, Zientek, Franziska, additional, Patt, Marianne, additional, Meyer, Philipp M., additional, Blüher, Matthias, additional, Strauß, Maria, additional, Fenske, Wiebke, additional, Hankir, Mohammed, additional, Ding, Yu-Shin, additional, Hilbert, Anja, additional, and Sabri, Osama, additional

Published
2017
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141. Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats

Author

Hankir, Mohammed K., primary, Seyfried, Florian, additional, Hintschich, Constantin A., additional, Diep, Thi-Ai, additional, Kleberg, Karen, additional, Kranz, Mathias, additional, Deuther-Conrad, Winnie, additional, Tellez, Luis A., additional, Rullmann, Michael, additional, Patt, Marianne, additional, Teichert, Jens, additional, Hesse, Swen, additional, Sabri, Osama, additional, Brust, Peter, additional, Hansen, Harald S., additional, de Araujo, Ivan E., additional, Krügel, Ute, additional, and Fenske, Wiebke K., additional

Published
2017
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142. Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Author

Hankir, Mohammed K., primary, Patt, Marianne, additional, Patt, Jörg T. W., additional, Becker, Georg A., additional, Rullmann, Michael, additional, Kranz, Mathias, additional, Deuther-Conrad, Winnie, additional, Schischke, Kristin, additional, Seyfried, Florian, additional, Brust, Peter, additional, Hesse, Swen, additional, Sabri, Osama, additional, Krügel, Ute, additional, and Fenske, Wiebke K., additional

Published
2017
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143. Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1–Deficient Mice

Author

Hankir, Mohammed K., primary, Kranz, Mathias, additional, Keipert, Susanne, additional, Weiner, Juliane, additional, Andreasen, Sille G., additional, Kern, Matthias, additional, Patt, Marianne, additional, Klöting, Nora, additional, Heiker, John T., additional, Brust, Peter, additional, Hesse, Swen, additional, Jastroch, Martin, additional, and Fenske, Wiebke K., additional

Published
2017
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144. Evaluation of early-phase [ 18 F]-florbetaben PET acquisition in clinical routine cases

Author

Daerr, Sonja, primary, Brendel, Matthias, additional, Zach, Christian, additional, Mille, Erik, additional, Schilling, Dorothee, additional, Zacherl, Mathias Johannes, additional, Bürger, Katharina, additional, Danek, Adrian, additional, Pogarell, Oliver, additional, Schildan, Andreas, additional, Patt, Marianne, additional, Barthel, Henryk, additional, Sabri, Osama, additional, Bartenstein, Peter, additional, and Rominger, Axel, additional

Published
2017
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145. In vitro and in vivo Human Metabolism of (S)-[18F]Fluspidine – A Radioligand for Imaging σ1 Receptors With Positron Emission Tomography (PET).

Author

Ludwig, Friedrich-Alexander, Fischer, Steffen, Houska, Richard, Hoepping, Alexander, Deuther-Conrad, Winnie, Schepmann, Dirk, Patt, Marianne, Meyer, Philipp M., Hesse, Swen, Becker, Georg-Alexander, Zientek, Franziska Ruth, Steinbach, Jörg, Wünsch, Bernhard, Sabri, Osama, and Brust, Peter

Subjects
POSITRON emission tomography, TRANSLOCATOR proteins, LIQUID chromatography-mass spectrometry
Abstract

(S)-[18F]fluspidine ((S)-[18F] 1) has recently been explored for positron emission tomography (PET) imaging of sigma-1 receptors in humans. In the current report, we have used plasma samples of healthy volunteers to investigate the radiometabolites of (S)-[18F] 1 and elucidate their structures with LC-MS/MS. For the latter purpose additional in vitro studies were conducted by incubation of (S)-[18F] 1 and (S)- 1 with human liver microsomes (HLM). In vitro metabolites were characterized by interpretation of MS/MS fragmentation patterns from collision-induced dissociation or by use of reference compounds. Thereby, structures of corresponding radio-HPLC-detected radiometabolites, both in vitro and in vivo (human), could be identified. By incubation with HLM, mainly debenzylation and hydroxylation occurred, beside further mono- and di-oxygenations. The product hydroxylated at the fluoroethyl side chain was glucuronidated. Plasma samples (10, 20, 30 min p.i., n = 5-6), obtained from human subjects receiving 250–300 MBq (S)-[18F] 1 showed 97.2, 95.4, and 91.0% of unchanged radioligand, respectively. In urine samples (90 min p.i.) the fraction of unchanged radioligand was only 2.6% and three major radiometabolites were detected. The one with the highest percentage, also found in plasma, matched the glucuronide formed in vitro. Only a small amount of debenzylated metabolite was detected. In conclusion, our metabolic study, in particular the high fractions of unchanged radioligand in plasma, confirms the suitability of (S)-[18F] 1 as PET radioligand for sigma-1 receptor imaging. [ABSTRACT FROM AUTHOR]

Published
2019
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146. Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls.

Author

Schinke, Christian, Hesse, Swen, Rullmann, Michael, Becker, Georg-Alexander, Luthardt, Julia, Zientek, Franziska, Patt, Marianne, Stoppe, Muriel, Schmidt, Elisa, Meyer, Klara, Meyer, Philipp M., Orthgieß, Johannes, Blüher, Matthias, Kratzsch, Jürgen, Ding, Yu-Shin, Then Bergh, Florian, and Sabri, Osama

Subjects
WEIGHT loss, OBESITY, CORTICOTROPIN releasing hormone, POSITRON emission tomography, ADRENOCORTICOTROPIC hormone
Abstract

The central noradrenaline (NA) stress-response network co-mediates hypothalamic-pituitary-adrenal (HPA) axis activation and arginine-vasopressin (AVP) release. Dysregulation of these systems contributes to stress-related diseases such as human obesity, but their interrelation remains unclear. The study was aimed to test for the first time in vivo whether central noradrenergic activity quantitatively indexed by the availability of the presynaptic NA transporter (NAT) is associated with HPA axis responsiveness as measured with the combined dexamethasone suppression/corticotropin releasing hormone stimulation (dex/CRH) test and copeptin as a surrogate marker of the serum AVP tone in highly obese, otherwise, healthy individuals compared to age- and sex-matched non-obese, healthy controls. In order to assess central NAT availability, positron emission tomography (PET) was applied using the NAT-selective radiotracer S,S-[11C]O-methylreboxetine (MRB) and correlated with curve indicators derived from the dex/CRH test (maximum, MAX, and area under the curve, AUC, for cortisol and adrenocorticotropic hormone, ACTH) as well as with copeptin. In non-obese controls, positive correlations were found between the NAT distribution volume ratios (DVR) of the orbitofrontal cortex (OFC) and the amygdala with the HPA response (OFC: ACTHMAXr = 0.87, p =.001; cortisolMAXr = 0.86, p =.002; amygdala: ACTHMAXr = 0.86, p =.002; cortisolMAXr = 0.79, p =.006), while in obesity, the hypothalamic DVR correlated inversely with the HPA axis response (cortisolMAX, r = −0.66, p =.04) and with copeptin (r = −0.71, p =.02). This association of central NAT availability with HPA axis responsiveness and copeptin suggests a mechanistic interaction between noradrenergic transmission with HPA axis activity and the serum AVP system that differs between non-obese individuals with prefrontal-limbic involvement and obesity with a hypothalamic-centered relationship. Whether the latter finding contributes to obesogenic behavior needs to be further explored. [ABSTRACT FROM AUTHOR]

Published
2019
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147. 18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION

Author

Brendel, Matthias, Barthel, Henryk, van Eimeren, Thilo, Marek, Ken, Beyer, Leonie, Song, Mengmeng, Palleis, Carla, Respondek, Gesine, Sauerbeck, Julia, Hammes, Jochen, Barbe, Michael, Onur, Oezguer A., Jessen, Frank, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Barret, Oliver, Madonia, Jennifer, Russell, David, Stephens, Andrew Wills, Roeber, Sigrun, Herms, Jochen, Boetzel, Kai, Levin, Johannes, Classen, Joseph, Höglinger, Günter, Bartenstein, Peter, Drzezga, Alexander, Seibyl, John, and Sabri, Osama

Published
2019
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148. Neurobehaviorale Korrelate der in vivo Serotonin- und Norepinephrin-Transporter-Verfügbarkeit bei Adipositas

Author

Bresch, Anke, Luthardt, Julia, Rullmann, Michael, Zientek, Franziska, Becker, Georg-Alexander, Patt, Marianne, Seese, Anita, Arelin, Kathrin, Lobsien, Donald, Hilbert, Anja, Blüher, Matthias, Faßhauer, Mathias, Stumvoll, Michael, Sabri, Osama, and Hesse, Swen

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Die Kontrolle von Impulsiven ist ein wichtiges zentraler Mechanismus adaptiven Verhaltens. Obwohl pharmako-klinische Studien eine serotonerg und noradrenerge Modulation impulsiven Verhaltens nahelegen, ist dieser Zusammenhang zwischen Impulsivität und der Verfügbarkeit der Noradrenalin-[for full text, please go to the a.m. URL], 4. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Essstörungen

Published
2014
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150. Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [18F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ1 Receptors

Author

Kranz, Mathias, primary, Sattler, Bernhard, additional, Wüst, Nathanael, additional, Deuther-Conrad, Winnie, additional, Patt, Marianne, additional, Meyer, Philipp, additional, Fischer, Steffen, additional, Donat, Cornelius, additional, Wünsch, Bernhard, additional, Hesse, Swen, additional, Steinbach, Jörg, additional, Brust, Peter, additional, and Sabri, Osama, additional

Published
2016
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