Effect Of (Z)-Isomer Content On [C-11]Abp688 Binding Potential In Humans

Purpose To determine how the low-affinity (Z)-isomer of the radiotracer [C-11]ABP688 affects binding potential values in vivo in humans.Methods High-resolution [C-11]ABP688 PET scans were acquired on 74 healthy volunteers (25 male, 49 female, mean age 203.0). The relative contents of (E)- and (Z)-isomers were determined prior to injection using analytical high-performance liquid chromatography [r(t)(E)=10min, r(t)(Z)=8.5min]. Mean binding potential [BPND=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.Results Mean +/- SD (E)-isomer content in [C-11]ABP688 production was 92 +/- 3.8% (range 78-97%). Percent (E)-isomer was positively correlated with BPND in the striatum (=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 BPND.Conclusions Even modest levels of (Z)-[C-11]ABP688 can reduce estimates of tracer binding in vivo. Future studies should use production methods that enrich levels of (E)-[C-11]ABP688, report tracer isomer ratios, and account for this factor in their analyses.