Evaluation of [¹¹C]UCB-A positron emission tomography in human brains

In preclinical studies, the positron emission tomography (PET) imaging with [¹¹C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [¹¹C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.

Twelve healthy subjects underwent 90-min baseline [¹¹C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [¹¹C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [¹¹C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.

[¹¹C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.