Fig. 3: ACI-19278 and ACI-19626 selectivity for TDP-43 over common co-pathologies.
From: Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology
a Autoradiography in Alzheimer’s disease (AD) tissue containing amyloid and Tau aggregates with an Aβ reference compound ([³H]Aβ ref cmpd) and Tau reference ligand ([³H]PI-2620). NSB: non-specific binding. Immunolabeling of adjacent sections with phospho-TDP-43 (orange), phospho-Tau (green) or Aβ (red) antibody. Scale bar, 2 mm. Representative autoradiograms from one donor from 3 independent experiments. b High-resolution autoradiography in the entorhinal cortex sections of an AD patient. [3H]PI-2620 included for reference. Thioflavin S staining in an adjacent section (left, green). Scale bar, 50 µm. Representative data of two independent experiments. c High-resolution autoradiography in FTLD-Tau tissue sections. Immunolabeling with phospho-Tau (top panels, green). Scale bar, 50 µm. Representative data of two donors tested in one experiment. d High-resolution autoradiography in tissue sections from a LATE-NC + ADNC case. Immunolabeling of the same sections with phospho-TDP-43 (orange), phospho-Tau (green), or Aβ (red) antibodies. Autoradiography images from adjacent sections with [3H]PI-2620 and [3H]Aβ reference compounds are shown on the bottom. Scale bar, 20 µm. Representative data of two donors tested in one experiment. White arrowheads: pTDP-43 pathology; red arrowheads: compound binding. e Saturation binding studies with [³H]ACI-19278 and [³H]ACI-19626 in brain homogenates from: From left to right, AD brain tissue containing Aβ and Tau aggregates (AD, insoluble fraction), AD brain tissue enriched for insoluble Tau paired helical filaments (AD, Tau PHF), and Parkinson’s disease (PD) brain tissue enriched for α-synuclein aggregates (PD, α -syn enriched). Reference ligands specific for Aβ (Aβ ref cmpd), Tau (PI-2620, Tau ref cmpd), and α-synuclein (ACI-12589, α-syn ref cmpd), respectively, were assessed in each homogenate. Representative data of at least two independent experiments for [³H]ACI-19278 and [³H]ACI-19626, and mean ± SD of three independent experiments for the [³H]Aβ ref cmpd in AD brain homogenates. Data from one out of two donors tested in independent experiments are shown for PHF and PD brain homogenates. Dotted line shows the limit under which binding is considered not relevant. Source data are provided as a Source Data file.
