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Effect of (Z)-isomer content on [11C]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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Fig. 1

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Acknowledgements

This work was supported by grants from the Canadian Institutes for Health Research MOP-133537 (ML), 119509 (CB and ML), 44072 (JRS) and 97910 (JRS); a grant from the Fonds de Recherche en Santé du Québec (FRQS) ERA-NET (ML); FRQS via fellowships and grants 981055 and 991027 (JRS); the Social Sciences and Humanities Research Council of Canada, grants 839-2000-1008 and 410-99-1048 (JRS); and the Fonds de recherche du Québec – Société et culture, grants 2002-RS-79238 and 2009-RG-124779 (JRS).

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Correspondence to Kelly Smart.

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The authors declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Research Ethics Board of the Montreal Neurological Institute, McGill University and the Ethics Committee of the CHU Sainte-Justine Research Center, and with the 1964 Helsinki Declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors.

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Smart, K., Cox, S.M.L., Kostikov, A. et al. Effect of (Z)-isomer content on [11C]ABP688 binding potential in humans. Eur J Nucl Med Mol Imaging 46, 1175–1178 (2019). https://doi.org/10.1007/s00259-018-4237-3

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  • DOI: https://doi.org/10.1007/s00259-018-4237-3

Keywords

  • Metabotropic glutamate receptors
  • mGluR5
  • Positron emission tomography
  • PET
  • [11C]ABP688