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

Purpose: To determine how the low-affinity (Z)-isomer of the radiotracer [¹¹C]ABP688 affects binding potential values in vivo in humans.

Methods: High-resolution [¹¹C]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.

Results: Mean ± SD (E)-isomer content in [¹¹C]ABP688 production was 92 ± 3.8% (range 78-97%). Percent (E)-isomer was positively correlated with BP_ND in the striatum (ρ = 0.28, p = 0.015) and limbic regions (ρ = 0.25, p = 0.036). In multiple regression analysis, sex (β = 0.39, p = 0.001) and (E)-isomer content (β = 0.23, p = 0.040) were significant predictors of BP_ND.

Conclusions: Even modest levels of (Z)-[¹¹C]ABP688 can reduce estimates of tracer binding in vivo. Future studies should use production methods that enrich levels of (E)-[¹¹C]ABP688, report tracer isomer ratios, and account for this factor in their analyses.