Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans

Abstract

Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [11C]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [11C]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution ( VT). Parametric maps were generated using the 1T model. [11C]UCB-J metabolized fairly quickly, with parent fraction of 36 ± 13% at 15 min after injection. Plasma free fraction was 32 ± 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. VT values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and VT values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on VT values. The mean absolute test-retest reproducibility for VT was 3-9% across regions. In conclusion, [11C]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.

Keywords: Brain imaging; kinetic modeling; neurodegeneration; positron emission tomography; synapses/dendrites.

Figures

Figure 1.

Radioactivity content in plasma after intravenous injection of [11C]UCB-J in human. (a) HPLC radiochromatograms of plasma content 3, 8, 15, 30, 60 and 90 min after [11C]UCB-J injection in volunteer 3 during test condition. (b) Total plasma radioactivity concentration over time (data are mean ± SD). (c) Unchanged [11C]UCB-J and radiometabolite fractions in plasma over time (data are mean ± SD). (d) [11C]UCB-J concentration in plasma over time (data are mean, 95% confidence interval is indicated with solid line for test and with dotted line for retest condition). *P < 0.05. SUV: standard uptake value.

Figure 2.

Template MR images (top) and aligned PET images of [11C]UCB-J during test (middle) and retest (bottom) condition. PET summation images (average of frames from 40 to 60 min) represent the mean of five subjects.

Figure 3.

Time course for regional brain radioactivity and curve fitting with the 1T (black solid line) and 2T (red dotted line) model in volunteer 1 during (a and b) test and (c and d) retest condition. SUV: standard uptake value.

Figure 4.

Individual MR images (left) and aligned parametric maps forK1 andVT of [11C]UCB-J using 1-tissue model and 120 min of PET data time during test and retest condition.

Figure 5.

Time stability analyses of outcome parametersK1 andVT. (a)K1 values and (b)VT values were calculated by 1T model and divided by the value measured using 120 min of PET data time. Data are means (n = 10), the SD was not displayed for the sake of clarity.