Cited by 944Neurotransmitter Receptor Influence on BehaviorMedical Imaging Techniques and ApplicationsNeuroscience and Neuropharmacology Research

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Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review

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Laruelle, Marc·2000·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1097/00004647-200003000-00001

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Abstract

Several groups have provided evidence that positron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuroreceptor imaging techniques might be applied to measure acute fluctuations in dopamine (DA) synaptic concentration in the living human brain. Competition between DA and radioligands for binding to D2 receptor is the principle underlying this approach. This new application of neuroreceptor imaging provides a dynamic measurement of neurotransmission that is likely to be informative to our understanding of neuropsychiatric conditions. This article reviews and discusses the body of data supporting the feasibility and potential of this imaging paradigm. Endogenous competition studies performed in rodents, nonhuman primates, and humans are first summarized. After this overview, the validity of the model underlying the interpretation of these imaging data is critically assessed. The current reference model is defined as the occupancy model, since changes in radiotracer binding potential (BP) are assumed to be directly caused by changes in occupancy of D2 receptors by DA. Experimental data supporting this model are presented. The evidence that manipulation of DA synaptic levels induces change in the BP of several D2 radiotracers (catecholamines and benzamides) is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The relationship between the magnitude of BP changes measured with PET or SPECT and the magnitude of changes in DA concentration measured by microdialysis supports the use of these noninvasive techniques to measure changes in neurotransmission. On the other hand, several observations remain unexplained. First, the amphetamine-induced changes in the BP of D2 receptor antagonists [123I]IBZM and [11C]raclopride last longer than amphetamine-induced changes in DA extracellular concentration. Second, nonbenzamide D2 receptor antagonists, such as spiperone and pimozide, are not affected by changes in DA release, or are affected in a direction opposite to that predicted by the occupancy model. Similar observations are reported with D1 radiotracers. These results suggest that the changes in BP following changes in DA concentration might not be fully accounted by a simple occupancy model. Specifically, the data are reviewed supporting that agonist-mediated receptor internalization might play an important role in characterizing receptor-ligand interactions. Finally, it is proposed that a better understanding of the mechanism underlying the effects observed with benzamides is essential to develop this imaging technique to other receptor systems.

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Molecular fMRI
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Self-citation
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Mapping the amphetamine-evoked dopamine release in the brain of the Gottingen minipig
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Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor ligand [123I]5‐I‐A‐85380
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Assessment of methylphenidate-induced changes in binding of continuously infused [11C]-raclopride in healthy human subjects: correlation with subjective effects
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“PET measurements, combined with amphetamine administration, have previously been used to investigate changes in synaptic DA concentrations in humans (Laruelle, 2000).”
Method
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In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates
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Authors: Laruelle, M.
Affiliations: New York State Psychiatric Institute (US)
Corresponding author: Laruelle, Marc
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2000-03
Volume: 20
Issue: 3
Pages: 423-451
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1097/00004647-200003000-00001
OpenAlex: W2054230322
Cited by: 944
References: 207
Citations by year: 2026: 6 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 15 · 2021: 26 · 2020: 18 · 2019: 28 · 2018: 26 · 2017: 31 · 2016: 31 · 2015: 36 · 2014: 54 · 2013: 47 · 2012: 36
FWCI: 4.78
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (K02MH01603-01, K02MH001603)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: dopamine D2 receptor, competitive binding, occupancy models, dopamine release, amphetamine, benzamide, receptor internalization, dopamine D1 receptor, microdialysis, SPECT
MeSH terms: Animals, Binding, Competitive, Brain, Dopamine, Humans, Ligands, Models, Neurological, Synaptic Transmission, Receptors, Dopamine, Tomography, Emission-Computed, Tomography, Emission-Computed, Single-Photon

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Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review

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