Ligand-based design of [<sup>18</sup>F]OXD-2314 for PET imaging in non-Alzheimer's disease tauopathies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38877019.
- Also identified by DOI 10.1038/s41467-024-49258-1 and PMC identifier 11178805.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Positron emission tomography (PET) imaging of tau aggregation in Alzheimer's disease (AD) is helping to map and quantify the in vivo progression of AD pathology. To date, no high-affinity tau-PET radiopharmaceutical has been optimized for imaging non-AD tauopathies. Here we show the properties of analogues of a first-in-class 4R-tau lead, [<sup>18</sup>F]OXD-2115, using ligand-based design. Over 150 analogues of OXD-2115 were synthesized and screened in post-mortem brain tissue for tau affinity against [<sup>3</sup>H]OXD-2115, and in silico models were used to predict brain uptake. [<sup>18</sup>F]OXD-2314 was identified as a selective, high-affinity non-AD tau PET radiotracer with favorable brain uptake, dosimetry, and radiometabolite profiles in rats and non-human primate and is being translated for first-in-human PET studies.
Medical subject headings
- Positron-Emission Tomography
- Tauopathies
- Brain
- Radiopharmaceuticals
- Alzheimer Disease
- Fluorine Radioisotopes
- tau Proteins