Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?

doi:10.3389/fnmol.2019.00255

Review

. 2019 Oct 18:12:255.

doi: 10.3389/fnmol.2019.00255. eCollection 2019.

Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?

Matthieu Colom^{1

2}, Benjamin Vidal¹, Luc Zimmer^{1

2

3}

Affiliations

¹ Lyon Neuroscience Research Center, INSERM, CNRS, Université de Lyon, Lyon, France.
² CERMEP, Hospices Civils de Lyon, Bron, France.
³ Institut National des Sciences et Techniques Nucléaires, CEA Saclay, Gif-sur-Yvette, France.

PMID: 31680859
PMCID: PMC6813225
DOI: 10.3389/fnmol.2019.00255

Review

Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?

Matthieu Colom et al. Front Mol Neurosci. 2019.

. 2019 Oct 18:12:255.

doi: 10.3389/fnmol.2019.00255. eCollection 2019.

Authors

Matthieu Colom^{1

2}, Benjamin Vidal¹, Luc Zimmer^{1

2

3}

Affiliations

¹ Lyon Neuroscience Research Center, INSERM, CNRS, Université de Lyon, Lyon, France.
² CERMEP, Hospices Civils de Lyon, Bron, France.
³ Institut National des Sciences et Techniques Nucléaires, CEA Saclay, Gif-sur-Yvette, France.

PMID: 31680859
PMCID: PMC6813225
DOI: 10.3389/fnmol.2019.00255

Abstract

Positron emission tomography (PET) is a molecular imaging modality that enables in vivo exploration of metabolic processes and especially the pharmacology of neuroreceptors. G protein-coupled receptors (GPCRs) play an important role in numerous pathophysiologic disorders of the central nervous system. Thus, they are targets of choice in PET imaging to bring proof concept of change in density in pathological conditions or in pharmacological challenge. At present, most radiotracers are antagonist ligands. In vitro data suggest that properties differ between GPCR agonists and antagonists: antagonists bind to receptors with a single affinity, whereas agonists are characterized by two different affinities: high affinity for receptors that undergo functional coupling to G-proteins, and low affinity for those that are not coupled. In this context, agonist radiotracers may be useful tools to give functional images of GPCRs in the brain, with high sensitivity to neurotransmitter release. Here, we review all existing PET radiotracers used from animals to humans and their role for understanding the ligand-receptor paradigm of GPCR in comparison with corresponding antagonist radiotracers.

Keywords: Positron emission tomography (PET); agonist; neuroimaging; radiopharmaceutical; receptor.

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Figures

**FIGURE 1**
Antagonist radioligands bind both coupled and non-coupled GPCRs with the same affinity. Agonist radioligands discriminate high-affinity (active GPCRs) versus low-affinity sites (inactive receptors).

**FIGURE 2**
Chemical structures of current agonist radiotracers of GPCRs. Dopamine receptors: (1) [¹¹C]SKF 82957, (2) [¹¹C]-SKF75670, (3) [¹¹C]SV-III-130, (4) [¹¹C]5-OH-DPAT, (5) [¹⁸F]5-OH-FPPAT, (6) [¹⁸F]FBu-AMC13 and derivatives, (7) [¹⁸F]FEt-AMC15 and derivatives, (8) [¹⁸F]AMC20, (9) [¹¹C]NPA, (10) [¹¹C]MNPA, (11) [¹⁸F]MCL-524, (12) [¹¹C]PHNO; serotonin receptors: (13) [¹¹C]CUMI-101, (14) [¹⁸F]F15599, (15) [¹⁸F]F13714, (16) [¹⁸F]F13640, (17) [¹¹C]Cimbi-5, (18) [¹¹C]Cimbi-36, (19) [¹⁸F]FECimbi-36; histamine receptors: (20) [¹¹C]MK-8278; cannabinoid receptors: (21) [¹¹C]OMAR or [¹¹C]JHU75528; (22) [¹⁸F]MK-9470, (23) [¹¹C]MePPEP, (24) [¹¹C]CB-119, (25) [¹¹C]PipISB, (26) [¹⁸F]PipISB, (27) [¹¹C]SD5024; acetylcholine receptors: (28) [¹⁸F]FP-TZTP; Opioïd receptors: (29) [¹¹C]carfentanil, (30) [¹¹C]PEO, (31) [¹¹C]GR103545, (32) [¹¹C]buprenorphine; Sigma 1 receptors: (33) [¹¹C]SA4503.

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References

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[1] Addy C., Wright H., Van Laere K., Gantz I., Erondu N., Musser B. J., et al. (2008). The Acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab. 7 68–78. 10.1016/j.cmet.2007.11.012 - DOI - PubMed

[2] Addy C., Wright H., Van Laere K., Gantz I., Erondu N., Musser B. J., et al. (2008). The Acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab. 7 68–78. 10.1016/j.cmet.2007.11.012 - DOI - PubMed

[3] Ahmad R., Goffin K., Van den Stock J., De Winter F.-L., Cleeren E., Bormans G., et al. (2014). In vivo type 1 cannabinoid receptor availability in Alzheimer’s disease. Eur. Neuropsychopharmacol. 24 242–250. 10.1016/j.euroneuro.2013.10.002 - DOI - PubMed

[4] Ahmad R., Goffin K., Van den Stock J., De Winter F.-L., Cleeren E., Bormans G., et al. (2014). In vivo type 1 cannabinoid receptor availability in Alzheimer’s disease. Eur. Neuropsychopharmacol. 24 242–250. 10.1016/j.euroneuro.2013.10.002 - DOI - PubMed

[5] Albizu L., Moreno J. L., Gonzalez-Maeso J., Sealfon S. C. (2010). Heteromerization of G protein-coupled receptors: relevance to neurological disorders and neurotherapeutics. CNS Neurol. Disord. Drug Targets 9 636–650. 10.2174/187152710793361586 - DOI - PMC - PubMed

[6] Albizu L., Moreno J. L., Gonzalez-Maeso J., Sealfon S. C. (2010). Heteromerization of G protein-coupled receptors: relevance to neurological disorders and neurotherapeutics. CNS Neurol. Disord. Drug Targets 9 636–650. 10.2174/187152710793361586 - DOI - PMC - PubMed

[7] Avissar S., Schreiber G. (2006). The involvement of G proteins and regulators of receptor–G protein coupling in the pathophysiology, diagnosis and treatment of mood disorders. Clin. Chim. Acta 366 37–47. 10.1016/j.cca.2005.11.003 - DOI - PubMed

[8] Avissar S., Schreiber G. (2006). The involvement of G proteins and regulators of receptor–G protein coupling in the pathophysiology, diagnosis and treatment of mood disorders. Clin. Chim. Acta 366 37–47. 10.1016/j.cca.2005.11.003 - DOI - PubMed

[9] Aznavour N., Rbah L., Riad M., Reilhac A., Costes N., Descarries L., et al. (2006). A PET imaging study of 5-HT1A receptors in cat brain after acute and chronic fluoxetine treatment. Neuroimage 33 834–842. 10.1016/j.neuroimage.2006.08.012 - DOI - PubMed

[10] Aznavour N., Rbah L., Riad M., Reilhac A., Costes N., Descarries L., et al. (2006). A PET imaging study of 5-HT1A receptors in cat brain after acute and chronic fluoxetine treatment. Neuroimage 33 834–842. 10.1016/j.neuroimage.2006.08.012 - DOI - PubMed

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Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?

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Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?

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