Effect of (Z)-isomer content on [${}^{11}$C]ABP688 binding potential in humans

To determine how the low-affinity (Z)-isomer of the radiotracer [${}^{11}$C]ABP688 affects binding potential values in vivo in humans. High-resolution [${}^{11}$C]ABP688 PET scans were acquired on 74 healthy volunteers (25 male, 49 female, mean age 20 ± 3.0). The relative contents of (E)- and (Z)-isomers were determined prior to injection using analytical high-performance liquid chromatography [r${}_t$(E) = 10 min, r${}_t$(Z) = 8.5 min]. Mean binding potential [BP${}_{ND}$ = f${}_{ND}$ * (B${}_{avail}$/K${}_D$)] values were calculated in the striatum, limbic regions, and prefrontal cortex using the simplified reference tissue model with cerebellar grey matter as reference. Mean ± SD (E)-isomer content in [${}^{11}$C]ABP688 production was 92 ± 3.8% (range 78–97%). Percent (E)-isomer was positively correlated with BP${}_{ND}$ in the striatum ($\rho$ = 0.28, p = 0.015) and limbic regions ($\rho$ = 0.25, p = 0.036). In multiple regression analysis, sex ($\beta$ = 0.39, p = 0.001) and (E)-isomer content ($\beta$ = 0.23, p = 0.040) were significant predictors of BP${}_{ND}$. Even modest levels of (Z)-[${}^{11}$C]ABP688 can reduce estimates of tracer binding in vivo. Future studies should use production methods that enrich levels of (E)-[${}^{11}$C]ABP688, report tracer isomer ratios, and account for this factor in their analyses.