Development and evaluation of [C]DPA-813 and [F]DPA-814: novel TSPO PET tracers insensitive to human single nucleotide polymorphism rs6971.

Purpose: The translocator protein 18 kDa (TSPO) is a widely used marker for imaging neuroinflammation via Positron Emission Tomography (PET). However, the vast majority of reported TSPO PET tracers display low binding affinity to a common isoform of human TSPO (rs6971; A147T), making them unsuitable for universal use in the general population. In this study, we have developed and preclinically validated two novel tracers designed to image TSPO in patients of all genotypes.

Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis.

The translocator protein (TSPO) is a biomarker for imaging neuroinflammation via Positron Emission Tomography (PET) across a broad range of CNS conditions. Most clinically used PET ligands targeting TSPO have limitations, including high lipophilicity and off-target binding or poor binding to a mutated TSPO isoform present in up to 30% of the population. Research efforts over the past decade have focused on development of improved TSPO PET radiotracers that overcome these limitations.