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Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

  • Eunkyung ParkEmail author
  • Jenna M. Sullivan
  • Beata Planeta
  • Jean-Dominique Gallezot
  • Keunpoong Lim
  • Shu-Fei Lin
  • Jim Ropchan
  • Timothy J. McCarthy
  • Yu-Shin Ding
  • Evan D. Morris
  • Wendol A. Williams
  • Yiyun Huang
  • Richard E. Carson
Original Article

Abstract

Purpose

[18F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test–retest reproducibility of [18F]FPEB in the human brain.

Methods

Seven healthy male subjects were scanned twice, 3 – 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [18F]FPEB. Four methods were used to estimate volume of distribution (V T): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test–retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V) were compared with arterial input (C A) to examine their usability in EQ analysis.

Results

Regional V T estimated by the four methods displayed a high degree of agreement (r 2 ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 – 12 % (CWM) and 7 – 9 % (CGM). Venous and arterial blood concentrations of [18F]FPEB were well matched during equilibrium (C V = 1.01 · C A, r 2 = 0.95).

Conclusion

[18F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [18F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.

Keywords

[18F]FPEB Human Metabotropic glutamate receptor 5 Positron emission tomography Reproducibility 

Notes

Acknowledgment

The authors thank the staff of the Yale University PET Center for their technical expertise and support.

Compliance with ethical standards

Funding

This study was supported by the Yale Pfizer Bioimaging Alliance. This study was also made possible by CTSA grant number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research.

Conflicts of interest

None.

Supplementary material

259_2015_3094_MOESM1_ESM.docx (118 kb)
ESM 1 (DOCX 117 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Eunkyung Park
    • 1
    Email author
  • Jenna M. Sullivan
    • 1
  • Beata Planeta
    • 1
  • Jean-Dominique Gallezot
    • 1
  • Keunpoong Lim
    • 1
  • Shu-Fei Lin
    • 1
  • Jim Ropchan
    • 1
  • Timothy J. McCarthy
    • 3
  • Yu-Shin Ding
    • 4
  • Evan D. Morris
    • 1
    • 2
  • Wendol A. Williams
    • 1
    • 2
  • Yiyun Huang
    • 1
  • Richard E. Carson
    • 1
  1. 1.PET Center, Department of Diagnostic RadiologyYale School of MedicineNew HavenUSA
  2. 2.Department of PsychiatryYale School of MedicineNew HavenUSA
  3. 3.Pfizer Worldwide Research and DevelopmentCambridgeUSA
  4. 4.Department of RadiologyNew York University School of MedicineNew YorkUSA

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