Skip to main content
SpringerLink
Log in

Test–retest reliability of [11C]AZ10419369 binding to 5-HT1B receptors in human brain

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[11C]AZ10419369 is a recently developed 5-HT1B receptor radioligand that is sensitive to changes in endogenous serotonin concentrations in the primate brain. Thus, [11C] AZ10419369 may serve as a useful tool in clinical studies of the pathophysiology and pharmacological treatment of diseases related to the serotonin system, such as depression and anxiety disorders. The aim of this study was to evaluate the test–retest reliability of [11C]AZ10419369.

Methods

Eight men were examined with PET and [11C] AZ10419369 twice on the same day. The binding potentials (BPND) of [11C]AZ10419369 in selected serotonergic projection areas and in the raphe nuclei (RN) were determined using the simplified reference tissue model, and for comparison also using a wavelet-aided parametric imaging approach. The BPND values obtained from the first and second PET scans were compared by means of descriptive statistics, difference, absolute variability and intraclass correlation coefficient.

Results

Similar BPND values were obtained with the two methods. The absolute mean differences in BPND between PET 1 and PET 2 were less than 3 % in all serotonergic projection regions. Absolute variabilities were low in cortical regions (5 – 7 %), low to moderate (7 – 14 %) in subcortical regions, but higher (20 %) in the RN.

Conclusion

The BPND of [11C]AZ10419369 is highly reproducible in cortical regions and satisfactory in subcortical projection areas. The variability in the RN is higher. Thus larger sample sizes or larger divergences are required to assess a potential difference between subjects or between experimental conditions in this region.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sari Y. Serotonin1B receptors: from protein to physiological function and behavior. Neurosci Biobehav Rev. 2004;28:565–82.

    Article  CAS  PubMed  Google Scholar 

  2. Ruf BM, Bhagwagar Z. The 5-HT1B receptor: a novel target for the pathophysiology of depression. Curr Drug Targets. 2009;10:1118–38.

    Article  CAS  PubMed  Google Scholar 

  3. Nicholson SL, Brotchie JM. 5-hydroxytryptamine (5-HT, serotonin) and Parkinson’s disease – opportunities for novel therapeutics to reduce the problems of levodopa therapy. Eur J Neurol. 2002;9 Suppl 3:1–6.

    Article  PubMed  Google Scholar 

  4. Varnas K, Jucaite A, McCarthy DJ, Stenkrona P, Nord M, Halldin C, et al. A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers. Cephalalgia. 2013;33:853–60.

    Article  PubMed  Google Scholar 

  5. Varnas K, Hall H, Bonaventure P, Sedvall G. Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem human brain using [3H]GR 125743. Brain Res. 2001;915:47–57.

    Article  CAS  PubMed  Google Scholar 

  6. Varnas K, Hurd YL, Hall H. Regional expression of 5-HT1B receptor mRNA in the human brain. Synapse. 2005;56:21–8.

    Article  PubMed  Google Scholar 

  7. Adell A, Celada P, Artigas F. The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. J Neurochem. 2001;79:172–82.

    Article  CAS  PubMed  Google Scholar 

  8. Varnas K, Nyberg S, Halldin C, Varrone A, Takano A, Karlsson P, et al. Quantitative analysis of [11C]AZ10419369 binding to 5-HT1B receptors in human brain. J Cereb Blood Flow Metab. 2011;31:113–23.

    Article  PubMed  Google Scholar 

  9. Pierson ME, Andersson J, Nyberg S, McCarthy DJ, Finnema SJ, Varnas K, et al. [11C]AZ10419369: a selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain. Neuroimage. 2008;41:1075–85.

    Article  PubMed  Google Scholar 

  10. Andersson JD, Pierson ME, Finnema SJ, Gulyas B, Heys R, Elmore CS, et al. Development of a PET radioligand for the central 5-HT1B receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds. Nucl Med Biol. 2011;38:261–72.

    Article  CAS  PubMed  Google Scholar 

  11. Finnema SJ, Varrone A, Hwang TJ, Gulyas B, Pierson ME, Halldin C, et al. Fenfluramine-induced serotonin release decreases [11C]AZ10419369 binding to 5-HT(1B)-receptors in the primate brain. Synapse. 2010;64:573–7.

    Article  CAS  PubMed  Google Scholar 

  12. Nord M, Finnema SJ, Halldin C, Farde L. Effect of a single dose of escitalopram on serotonin concentration in the non-human and human primate brain. Int J Neuropsychopharmacol. 2013;16:1577–86.

    Article  CAS  PubMed  Google Scholar 

  13. Finnema SJ, Varrone A, Hwang TJ, Halldin C, Farde L. Confirmation of fenfluramine effect on 5-HT(1B) receptor binding of [11C]AZ10419369 using an equilibrium approach. J Cereb Blood Flow Metab. 2012;32:685–95.

    Article  CAS  PubMed  Google Scholar 

  14. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;20(59 Suppl):22–33; quiz 4–57.

    PubMed  Google Scholar 

  15. Derry C, Benjamin C, Bladin P, le Bars D, Tochon-Danguy H, Berkovic SF, et al. Increased serotonin receptor availability in human sleep: evidence from an [18F]MPPF PET study in narcolepsy. Neuroimage. 2006;30:341–8.

    Article  PubMed  Google Scholar 

  16. Varrone A, Sjoholm N, Eriksson L, Gulyas B, Halldin C, Farde L. Advancement in PET quantification using 3D-OP-OSEM point spread function reconstruction with the HRRT. Eur J Nucl Med Mol Imaging. 2009;36:1639–50.

    Article  PubMed  Google Scholar 

  17. Schain M, Toth M, Cselenyi Z, Stenkrona P, Halldin C, Farde L, et al. Quantification of serotonin transporter availability with [11C] MADAM – a comparison between the ECAT HRRT and HR systems. Neuroimage. 2012;60:800–7.

    Article  CAS  PubMed  Google Scholar 

  18. Bonaventure P, Schotte A, Cras P, Leysen JE. Autoradiographic mapping of 5-HT1B- and 5-HT1D receptors in human brain using [3H]alniditan, a new radioligand. Receptors Channels. 1997;5:225–30.

    CAS  PubMed  Google Scholar 

  19. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–9.

    Article  CAS  PubMed  Google Scholar 

  20. Cselenyi Z, Olsson H, Farde L, Gulyas B. Wavelet-aided parametric mapping of cerebral dopamine D2 receptors using the high affinity PET radioligand [11C]FLB 457. Neuroimage. 2002;17:47–60.

    Article  PubMed  Google Scholar 

  21. McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychol Methods. 1996;1:30–46.

    Article  Google Scholar 

  22. Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86:420–8.

    Article  CAS  PubMed  Google Scholar 

  23. Alakurtti K, Aalto S, Johansson JJ, Nagren K, Tuokkola T, Oikonen V, et al. Reproducibility of striatal and thalamic dopamine D2 receptor binding using [11C]raclopride with high-resolution positron emission tomography. J Cereb Blood Flow Metab. 2011;31:155–65.

    Article  CAS  PubMed  Google Scholar 

  24. Lundberg J, Halldin C, Farde L. Measurement of serotonin transporter binding with PET and [11C]MADAM: a test-retest reproducibility study. Synapse. 2006;60:256–63.

    Article  CAS  PubMed  Google Scholar 

  25. Hirvonen J, Kajander J, Allonen T, Oikonen V, Nagren K, Hietala J. Measurement of serotonin 5-HT1A receptor binding using positron emission tomography and [carbonyl-(11)C]WAY-100635 – considerations on the validity of cerebellum as a reference region. J Cereb Blood Flow Metab. 2007;27:185–95.

    Article  CAS  PubMed  Google Scholar 

  26. Jovanovic H, Cerin A, Karlsson P, Lundberg J, Halldin C, Nordstrom AL. A PET study of 5-HT1A receptors at different phases of the menstrual cycle in women with premenstrual dysphoria. Psychiatry Res. 2006;148:185–93.

    Article  CAS  PubMed  Google Scholar 

  27. Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM. 5-HT radioligands for human brain imaging with PET and SPECT. Med Res Rev. 2013;33:54–111.

    Article  CAS  PubMed  Google Scholar 

  28. Selvaraj S, Turkheimer F, Rosso L, Faulkner P, Mouchlianitis E, Roiser JP, et al. Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. Mol Psychiatry. 2012;17:1254–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Katarina Varnäs for her generous help in calculating the ICCs. We also thank the other members of the PET group at the Karolinska Institutet for their close assistance during this study.

Conflicts of interest

L.F. is an employee of AstraZeneca and affiliated with KI. C.H. has a consultancy agreement with AstraZeneca. M.N., S.F. and M.S. declare no conflicts of interest. The research leading to these results also received support from the Swedish Research Council under grant K2012-61X-09114-23-4 to L.F. and from the Innovative Medicine Initiative Joint Undertaking under grant agreement n° 115008 of which resources are composed of EFPIA in‐kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007‐2013).

Author information

Authors and Affiliations

  1. Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatric Research, R5:00, Karolinska University Hospital, SE-17176, Stockholm, Sweden

    Magdalena Nord, Sjoerd J. Finnema, Martin Schain, Christer Halldin & Lars Farde

Authors
  1. Magdalena Nord
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sjoerd J. Finnema
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Schain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christer Halldin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lars Farde
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Magdalena Nord.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 13.5 kb)

Fig. S1

(JPEG 39 kb)

High resolution image (TIFF 827 kb)

Fig. S2

(JPEG 13 kb)

High resolution image (TIFF 270 kb)

Table S1

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nord, M., Finnema, S.J., Schain, M. et al. Test–retest reliability of [11C]AZ10419369 binding to 5-HT1B receptors in human brain. Eur J Nucl Med Mol Imaging 41, 301–307 (2014). https://doi.org/10.1007/s00259-013-2529-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-013-2529-1

Keywords

Search

Navigation