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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Acknowledgment

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

Compliance with ethical standards

ᅟ

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.

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Authors and Affiliations

  1. PET Center, Department of Diagnostic Radiology, Yale School of Medicine, 801 Howard Avenue, PO Box 208048, New Haven, CT, 06520-8048, USA

    Eunkyung Park, Jenna M. Sullivan, Beata Planeta, Jean-Dominique Gallezot, Keunpoong Lim, Shu-Fei Lin, Jim Ropchan, Evan D. Morris, Wendol A. Williams, Yiyun Huang & Richard E. Carson

  2. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA

    Evan D. Morris & Wendol A. Williams

  3. Pfizer Worldwide Research and Development, Cambridge, MA, USA

    Timothy J. McCarthy

  4. Department of Radiology, New York University School of Medicine, New York, NY, USA

    Yu-Shin Ding

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  1. Eunkyung Park
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  2. Jenna M. Sullivan
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Correspondence to Eunkyung Park.

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Park, E., Sullivan, J.M., Planeta, B. et al. Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans. Eur J Nucl Med Mol Imaging 42, 1530–1541 (2015). https://doi.org/10.1007/s00259-015-3094-6

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  • DOI: https://doi.org/10.1007/s00259-015-3094-6

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