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  Additive value of [18 F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Katzdobler, S., Nitschmann, A., Barthel, H., Bischof, G., Beyer, L., Marek, K., et al. (2022). Additive value of [18 F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome. European Journal of Nuclear Medicine and Molecular Imaging. doi:10.1007/s00259-022-05964-w.

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 Creators:
Katzdobler, Sabrina1, 2, 3, Author
Nitschmann, Alexander4, Author
Barthel, Henryk5, Author
Bischof, Gerard6, 7, Author
Beyer, Leonie4, Author
Marek, Ken8, 9, Author
Song, Mengmeng4, Author
Wagemann, Olivia1, 2, Author
Palleis, Carla1, 2, 3, Author
Weidinger, Endy1, 2, Author
Nack, Anne1, Author
Fietzek, Urban1, Author
Kurz, Carolin10, Author
Häckert, Jan10, 11, Author
Stapf, Theresa10, Author
Ferschmann, Christian4, Author
Scheifele, Maximilian4, Author
Eckenweber, Florian4, Author
Biechele, Gloria4, Author
Franzmeier, Nicolai12, Author
Dewenter, Anna12, AuthorSchönecker, Sonja1, AuthorSaur, Dorothee13, AuthorSchroeter, Matthias L.14, 15, 16, Author           Rumpf, Jost-Julian13, AuthorRullmann, Michael5, AuthorSchildan, Andreas5, AuthorPatt, Marianne5, AuthorStephens, Andrew W17, Authorvan Eimeren, Thilo6, AuthorNeumaier, Bernd6, 18, AuthorDrzezga, Alexander6, 7, 19, AuthorDanek, Adrian1, 2, AuthorClassen, Joseph13, AuthorBürger, Katharina12, AuthorJanowitz, Daniel12, AuthorRauchmann, Boris-Stephan11, 20, AuthorStöcklein, Sophia20, AuthorPerneczky, Robert2, 3, 11, 21, AuthorSchöberl, Florian1, AuthorZwergal, Andreas1, AuthorHöglinger, Günter U2, 3, 22, AuthorBartenstein, Peter3, 4, AuthorVillemagne, Victor23, 24, 25, AuthorSeibyl, John8, 9, AuthorSabri, Osama5, AuthorLevin, Johannes1, 2, 3, AuthorBrendel, Matthias26, 27, 28, Author more..
Affiliations:
1Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany, ou_persistent22              
2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany, ou_persistent22              
3Munich Cluster for Systems Neurology (SyNergy), Munich, Germany, ou_persistent22              
4Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany, ou_persistent22              
5Department of Nuclear Medicine, University Hospital of Leipzig, Leipzig, Germany, ou_persistent22              
6Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany, ou_persistent22              
7Molecular Organization of the Brain, Institute for Neuroscience and Medicine, INM-2), Jülich, Germany, ou_persistent22              
8InviCRO, LLC, Boston, MA, USA, ou_persistent22              
9Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA, ou_persistent22              
10Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany, ou_persistent22              
11Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, BKH Augsburg, Augsburg, Germany, ou_persistent22              
12Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany, ou_persistent22              
13Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany, ou_persistent22              
14Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany, ou_persistent22              
15LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany, ou_persistent22              
16Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
17Life Molecular Imaging GmbH, Berlin, Germany, ou_persistent22              
18Institute for Neuroscience and Medicine (INM-3), Cognitive Neuroscience, Research Centre Juelich, Juelich, Germany, ou_persistent22              
19German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, ou_persistent22              
20Department of Radiology, University Hospital of Munich, LMU Munich, Munich, Germany, ou_persistent22              
21Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College, London, UK, ou_persistent22              
22Department of Neurology, Hannover Medical School, Hannover, Germany, ou_persistent22              
23Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, VIC, Australia, ou_persistent22              
24Department of Medicine, Austin Health, The University of Melbourne, Melbourne, VIC, Australia, ou_persistent22              
25Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA, ou_persistent22              
26German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. matthias.brendel@med.uni-muenchen.de, ou_persistent22              
27Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. matthias.brendel@med.uni-muenchen.de, ou_persistent22              
28 Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. matthias.brendel@med.uni-muenchen.de, ou_persistent22              

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Free keywords: Neuronal injury; PET; Perfusion; Tau; [18F]PI-2620
 Abstract: Purpose: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs.

Methods: Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0-60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living).

Results: Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = - 0.431; p = 0.0005).

Conclusion: [18F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.

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Language(s): eng - English
 Dates: 2022-01-172022-09-012022-09-14
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1007/s00259-022-05964-w
Other: online ahead of print
PMID: 36102964
 Degree: -

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Project name : -
Grant ID : 01EK1605A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : SCHR 774/5–1
Funding program : -
Funding organization : German Research Foundation (DFG)

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Title: European Journal of Nuclear Medicine and Molecular Imaging
  Other : Eur. J. Nucl. Med. Mol. Imaging
Source Genre: Journal
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Publ. Info: Heidelberg, Germany : Springer-Verlag
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1619-7070
CoNE: https://pure.mpg.de/cone/journals/resource/954925519624