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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84337 |
| Date | 27 March 2023 |
| Creators | 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, Günther U., Bartenstein, Peter, Herms, Jochen, Brendel, Matthias, Beyer, Leonie |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-2295, 684523 |
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