Given the recent regulatory approvals of PET radiopharmaceuticals for imaging tau burden in the AD brain, several radiotracers have been repurposed to evaluate tau in non-AD tauopathies [1, 3]. However, interpretation of imaging results for non-AD tau burden with these tracers can be non-trivial [14], demonstrating the differences in tau distribution, isoforms, and folding patterns between diseases. [18F]OXD-2314 is a promising alternative PET radiopharmaceutical designed specifically for its high in vitro affinity to tau from non-AD tauopathies, and possesses an alternate binding site to tau aggregates compared to other tau tracers [10].

High quality images were obtained by PET/CT following injection of ~ 190 MBq of [18F]OXD-2314, and no adverse effects were reported in any subject following tracer administration. The radiopharmaceutical had good stability in vivo, with 50–60% remaining [18F]OXD-2314 in plasma at 110 min post-injection. The radiometabolite fraction was more polar than the parent radiotracer [18F]OXD-2314, suggesting limited brain permeability of these radiometabolites, as was observed in rodent brain homogenates [10]. Though sex differences were observed in radiometabolites of preclinical species, no sex differences have been observed in humans; albeit both instances suffer from low-powered data.

Kinetic modelling of [18F]OXD-2314 indicates reversible behaviour of brain uptake in healthy humans with dynamics similar to that of preclinical PET imaging studies carried out in mouse, rat, macaque, and baboon [10], demonstrating fast uptake into the brain and washout over the course of the scan. No preferential binding to any region indicative of the presence of tau-specific binding was observed in these healthy participants, though potential contributions of off-target or non-specific binding cannot be excluded, as suggested by the higher baseline VT in the basal ganglia identified by both VOI and voxelwise measurements. In addition, it is important to note that the TAC's reversible behaviour by conforming to the 2-TCM could be due to slow non-specific interactions, and the observed reversibility alone is not indicative of specific binding. Lastly, our preliminary results suggest that PET acquisition time may be reduced to 90 min while maintaining quantification bias below 5%; however, the reduction in acquisition time must be confirmed using data acquired from participants with tauopathies.

Further evaluation of [18F]OXD-2314 in humans is underway, including: test-retest reliability, whole body dosimetry, and kinetic modelling and evaluation of reference regions in populations with tau accumulation.