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Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [11C]FLB 457 PET study

Molecular Psychiatry volume 19, pages 302–310 (2014)Cite this article

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A Corrigendum to this article was published on 23 April 2013

Abstract

In a recent human positron emission tomography (PET) study we demonstrated the ability to detect amphetamine-induced dopamine (DA) release in the prefrontal cortex as a reduction in the binding of the DA D2/3 radioligand [11C]FLB 457. A key requirement for validating this paradigm for use in clinical studies is demonstrating that the changes in [11C]FLB 457 binding observed with PET following amphetamine are related to changes in dialysate DA concentration as measured with microdialysis. Microdialysis and PET experiments were performed to compare, in five rhesus monkeys, amphetamine-induced DA release and [11C]FLB 457 displacement in the frontal cortex after three doses of amphetamine (0.3 mg kg−1, 0.5 mg kg−1 and 1.0 mg kg−1). Amphetamine led to a significant dose-dependent increase in dialysate (0.3 mg kg−1: 999±287%; 0.5 mg kg−1: 1320±432%; 1.0 mg kg−1: 2355±1026%) as measured with microdialysis and decrease in [11C]FLB 457 binding potential (BPND, 0.3 mg kg−1: −6±6%; 0.5 mg kg−1: −16±4%; 1.0 mg kg−1: −24±2%) as measured with PET. The relationship between amphetamine-induced peak ΔDA and Δ[11C]FLB 457 BPND in the frontal cortex was linear. The results of this study clearly demonstrate that the magnitude of dialysate DA release is correlated with the magnitude of the reduction in [11C]FLB 457 BPND in the frontal cortex. The use of the [11C]FLB 457-amphetamine imaging paradigm in humans should allow for characterization of prefrontal cortical DA release in neuropsychiatric disorders such as schizophrenia and addiction.

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Acknowledgements

The project described was supported by Award Number DA026472, DA025636, AA0188330, and BLR&D 1IO1BX000782 from the National Institute on Drug Abuse (NIDA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), and Veterans Administration (VA).

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDA, NIAAA or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA

    R Narendran, B J Lopresti, N S Mason, J Ruszkiewicz, C-M Chen, L Deuitch & W G Frankle

  2. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    R Narendran, H P Jedema, K Gurnsey, W G Frankle & C W Bradberry

  3. VA Pittsburgh Health Services, Pittsburgh, PA, USA

    C W Bradberry

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Correspondence to R Narendran.

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Dr Narendran's imaging group has done contractual research work at the University of Pittsburgh for GlaxoSmithKline Inc. and ONO Pharmaceutical Co., LTD.

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Narendran, R., Jedema, H., Lopresti, B. et al. Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [11C]FLB 457 PET study. Mol Psychiatry 19, 302–310 (2014). https://doi.org/10.1038/mp.2013.9

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