Development of [¹⁸F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology.

ABSTRACT: Aggregated TDP-43 is a hallmark of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and limbic-predominant age-related TDP-43 encephalopathy (LATE), and a common co-pathology in other neurodegenerative diseases. Currently, no specific biomarkers exist to assess TDP-43 pathology in vivo. We developed two small-molecule radiopharmaceuticals, [¹⁸F]ACI-19278 and [¹⁸F]ACI-19626, for visualizing TDP-43 inclusions by positron emission tomography (PET). Both ligands bind with high affinity to aggregated, but not soluble, TDP-43 in patient brain samples from diverse TDP-43 proteinopathies, including frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), ALS, and LATE, and in cell models. Both compounds display excellent selectivity for TDP-43 ov

SUBMITTER: Vokali E 

PROVIDER: S-EPMC12552610 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature