Skip to main content

Positron Emission Tomography (PET) Imaging of Metabotropic Glutamate Receptor Subtype 2 (mGlu2) Based on a Negative Allosteric Modulator Radioligand

  • Protocol
  • First Online:
Metabotropic Glutamate Receptor Technologies

Part of the book series: Neuromethods ((NM,volume 164))

Abstract

Metabotropic glutamate receptor subtype 2 (mGlu2) is a G-protein-coupled receptor and involved in the physiopathology of several major mental disorders and neurodegenerative diseases. Nowadays, with the development of positron emission tomography (PET) tracers, the distribution and concentration of mGlu2 in vivo can be quantitatively evaluated, which could substantially facilitate disease diagnosis and drug discovery. To demonstrate continuous efforts in the development of mGlu2 PET tracers, we present an example with detailed protocols, including step-by-step procedures of chemical synthesis of an mGlu2-negative allosteric modulator, namely 7-((2,5-dioxopyrrolidin-1-yl)methyl)-4-(2-fluro-4-methoxyphenyl) quinoline-2-carboxamide (QCA), radiolabeling of [11C]QCA, ex vivo whole-body biodistribution, autoradiography, and dynamic PET imaging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322

    Article  CAS  Google Scholar 

  2. Rondard P, Pin JP (2015) Dynamics and modulation of metabotropic glutamate receptors. Curr Opin Pharmacol 20:95–101

    Article  CAS  Google Scholar 

  3. Lindsley CW, Emmitte KA, Hopkins CR, Bridges TM, Gregory KJ, Niswender CM, Conn PJ (2016) Practical strategies and concepts in GPCR allosteric modulator discovery: recent advances with metabotropic glutamate receptors. Chem Rev 116(11):6707–6741

    Article  CAS  Google Scholar 

  4. Celanire S, Sebhat I, Wichmann J, Mayer S, Schann S, Gatti S (2015) Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005—present). Expert Opin Ther Pat 25:69

    Article  CAS  Google Scholar 

  5. Melancon BJ et al (2012) Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J Med Chem 55(4):1445–1464

    Article  CAS  Google Scholar 

  6. Trabanco AA, Cid JM (2013) mGluR2 positive allosteric modulators: a patent review (2009—present). Expert Opin Ther Pat 23:629

    Article  CAS  Google Scholar 

  7. O’Brien DE et al (2018) Differential pharmacology and binding of mGlu2 receptor allosteric modulators. Mol Pharmacol 93(5):526–540

    Article  Google Scholar 

  8. Acri JB, Cross AJ, Skolnick P (2017) From bench to bedside: mGluR2 positive allosteric modulators as medications to treat substance use disorders. Psychopharmacology 234(9–10):1347–1355

    Article  CAS  Google Scholar 

  9. Harpsøe K et al (2015) Selective negative allosteric modulation of metabotropic glutamate receptors—a structural perspective of ligands and mutants. Sci Rep 5:13869

    Article  Google Scholar 

  10. Pike VW (2016) Considerations in the development of reversibly binding PET Radioligands for brain imaging. Curr Med Chem 23(18):1818–1869

    Article  CAS  Google Scholar 

  11. Phelps ME (2000) Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 97(16):9226–9233

    Article  CAS  Google Scholar 

  12. Deng X, Rong J, Wang L, Vasdev N, Zhang L, Josephson L, Liang SH (2019) Chemistry for positron emission tomography: recent advances in 11C-, 18F-, 13N-, and 15O-labeling reactions. Angew Chem Int Ed 58(9):2580–2605

    Article  CAS  Google Scholar 

  13. Ametamey SM, Honer M, Schubiger PA (2008) Molecular imaging with PET. Chem Rev 108(5):1501–1516

    Article  CAS  Google Scholar 

  14. Miller PW, Long NJ, Vilar R, Gee AD (2008) Synthesis of 11C, 18F, 15O, and 13N radiolabels for positron emission tomography. Angew Chem Int Ed Eng 47(47):8998–9033

    Article  CAS  Google Scholar 

  15. Fowler JS, Wolf AP (1997) Working against time: rapid radiotracer synthesis and imaging the human brain. Acc Chem Res 30:181

    Article  CAS  Google Scholar 

  16. Wang JQ, Zhang Z, Kuruppu D, Brownell AL (2012) Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo. Bioorg Med Chem Lett 22:1958

    Article  CAS  Google Scholar 

  17. Wang JQ, Kuruppu D, Brownell AL (2008) Radiosynthesis of the mGluR2/3 PET tracer (S,S,S)-2-(2-carboxycyclopropyl)-2-(4-[11C]methoxyphenethyl)glycine dimethyl ester ([11C]CMG). J Nucl Med 49:286P

    Google Scholar 

  18. Celen S et al (2012) Preliminary biological evaluation of [11C]JNJ42491293 as a radioligand for PET imaging of mGluR2 in brain. J Nucl Med 53:286

    Google Scholar 

  19. Andres JI et al (2012) Synthesis, evaluation, and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging. J Med Chem 55(20):8685–8699

    Article  CAS  Google Scholar 

  20. Majo V, Prabhakaran J, Simpson N, Arango V, Mann JJ, Kumar JD (2013) Development of a [18F]-labeled positive allosteric modulator of the metabotropic glutamate receptor 2 (mGluR2) as a potential PET tracer. J Nucl Med 54(Suppl 2):1072

    Google Scholar 

  21. Ma Y et al (2017) Synthesis and evaluation of 1-(cyclopropylmethyl)-4-(4-[11C]methoxyphenyl)-piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([11C]CMDC) for PET imaging of metabotropic glutamate receptor 2 in the rat brain. Biorg Med Chem 25(3):1014–1021

    Article  CAS  Google Scholar 

  22. Zhang X et al (2017) Synthesis and preliminary studies of a novel negative allosteric modulator, 7-((2,5-Dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[(11)C]methoxyphenyl) quinoline-2-carboxamide, for imaging of metabotropic glutamate receptor 2. ACS Chem Neurosci 8(9):1937–1948

    Article  CAS  Google Scholar 

  23. Yamasaki T, Zhang X et al (2020) Identification and development of a new positron emission tomography ligand 4-(2-Fluoro-4-[11C]methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide for imaging metabotropic glutamate receptor subtype 2 (mGlu2). J Med Chem 63(20):11469–11483

    Google Scholar 

  24. Zhang X, Zhang Y et al (2020) Synthesis and preliminary studies of 11C-labeled tetrahydro-1,7-naphthyridine-2-carboxamides for PET imaging of metabotropic glutamate receptor 2. Theranostics 10(24):11178–11196

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Steven H. Liang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Zhang, X. et al. (2021). Positron Emission Tomography (PET) Imaging of Metabotropic Glutamate Receptor Subtype 2 (mGlu2) Based on a Negative Allosteric Modulator Radioligand. In: Olive, M.F., Burrows, B.T., Leyrer-Jackson, J.M. (eds) Metabotropic Glutamate Receptor Technologies. Neuromethods, vol 164. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1107-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1107-4_2

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1106-7

  • Online ISBN: 978-1-0716-1107-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics