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Πέμπτη 3 Ιανουαρίου 2019

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

Abstract

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 [rt(E) = 10 min, rt(Z) = 8.5 min]. Mean binding potential [BPND = fND * (Bavail/KD)] 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 BPND 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 BPND.

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.



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