1 Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, QC, H3A 1A1, Canada. kelly.smart@mail.mcgill.ca.
2 Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, QC, H3A 1A1, Canada.
3 Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
4 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
5 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
6 Institute of Mental Health Research, affiliated with the University of Ottawa, Ottawa, ON, K1Z 7K4, Canada.
7 Department of Psychology, Université Laval, Laval, QC, G1V 0A6, Canada.
8 CHU Ste-Justine Research Center, Montreal, QC, H3T 1C5, Canada.
9 Department of Psychiatry and Addiction, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
10 Department of Psychology, McGill University, Montreal, QC, H3G 1G1, Canada.
11 Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, H4B 1R6, Canada.

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

Eur J Nucl Med Mol Imaging. 2019 May;46(5):1175-1178

Authors: Smart K, Cox SML, Kostikov A, Shalai A, Scala SG, Tippler M, Jaworska N, Boivin M, Séguin JR, Benkelfat C, Leyton M

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 (??=?0.28, p?=?0.015) and limbic regions (??=?0.25, p?=?0.036). In multiple regression analysis, sex (ß?=?0.39, p?=?0.001) and (E)-isomer content (ß?=?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.

PMID: 30607444 [PubMed - in process]