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Reproducibility of Non-Invasive A1 Adenosine Receptor Quantification in the Rat Brain Using [18F]CPFPX and Positron Emission Tomography

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Abstract

Purpose

The A1AR antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]CPFPX) has recently been shown to be a suitable radiotracer for quantitative in vivo imaging of the A1 adenosine receptor (A1AR) in rats. The present study evaluates the reproducibility of non-invasive longitudinal A1AR studies with [18F]CPFPX and a dedicated small animal positron emission tomography (PET) scanner.

Procedures

Twelve male Sprague Dawley rats underwent four repeated dynamic PET scans with a bolus injection of [18F]CPFPX. A1AR availability was determined by different non-invasive approaches including simplified and multilinear reference tissue (olfactory bulb)-based models and graphical methods. The outcome parameter binding potential (BP) was evaluated in terms of variability and reproducibility.

Results

Repeated estimations of [18F]CPFPX BP ND gave reliable results with acceptable variability (mean 12 %) and reproducibility (intraclass correlation coefficients raging from 0.57 to 0.68) in cortical and subcortical regions of the rat brain. With regard to kinetic models, test-retest stability of the simplified reference-tissue model (SRTM) was superior to multilinear and graphical approaches.

Conclusions

Non-invasive quantification of A1AR density in the rat brain is reproducible and reliable with [18F]CPFPX PET and allows longitudinal designs of in vivo imaging studies in rodents.

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References

  1. Paul S, Elsinga HP, Ishiwata K, Dierckx RAJO, van Waarde A (2011) Adenosine A1 receptors in the central nervous system: their functions in health and disease, and possible elucidation by PET imaging. Curr Med Chem 18:4820–4835

    Article  PubMed  CAS  Google Scholar 

  2. Elmenhorst D, Meyer PT, Matusch A et al (2007) Test-retest stability of cerebral A1 adenosine receptor quantification using [18F]CPFPX and PET. Eur J Nucl Med Mol Imaging 34:1061–1070

    Article  PubMed  CAS  Google Scholar 

  3. Meyer PT, Bier D, Hoschbach MH et al (2004) Quantification of cerebral A1 adenosine receptors in humans using [18F]CPFPX and PET. J Cereb Blood Flow Metab 24:323–333

    Article  PubMed  CAS  Google Scholar 

  4. Elmenhorst D, Kroll T, Wedekind F et al (2013) In vivo kinetic and steady-state quantification of 18F-CPFPX binding to rat cerebral A1 adenosine receptors: validation by displacement and autoradiographic experiments. J Nucl Med 54:1–9

    Article  Google Scholar 

  5. Christie MA, McKenna JT, Connolly NP, McCarley RW, Strecker RE (2008) 24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task. J Sleep Res 17:376–384

    Article  PubMed  PubMed Central  Google Scholar 

  6. Holschbach MH, Olsson RA, Bier D et al (2002) Synthesis and evaluation of no-carrier-added 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F]CPFPX): a potent and selective A1-adenosine receptor antagonist for in vivo imaging. J Med Chem 45:5150–5156

    Article  PubMed  CAS  Google Scholar 

  7. Innis RB, Cunningham VJ, Delforge J et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539

    Article  PubMed  CAS  Google Scholar 

  8. Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. Neuroimage 4:153–158

    Article  PubMed  CAS  Google Scholar 

  9. Ichise M, Loiw JS, Lu JQ et al (2003) Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J Cereb Blood Flow Metab 23:1096–1112

    Article  PubMed  Google Scholar 

  10. Wu Y, Carson RE (2002) Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab 22:1440–1452

    Article  PubMed  Google Scholar 

  11. Logan J, Fowler JS, Volkow ND et al (1996) Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab 16:834–840

    Article  PubMed  CAS  Google Scholar 

  12. Elmenhorst D, Aliaga A, Bauer A, Rosa-Neto P (2012) Test-retest stability of cerebral mGluR5 quantification using [11C]ABP688 and positron emission tomography in rats. Synapse 66:552–560

    Article  PubMed  CAS  Google Scholar 

  13. Weir JP (2005) Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res 19:231–240

    PubMed  Google Scholar 

  14. Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191

    Article  PubMed  Google Scholar 

  15. Xie X, Ramkumar V, Toth LA (2007) Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Comp Med 57:538–545

    PubMed  CAS  Google Scholar 

  16. Collins LE, Galtieri DJ, Collins P et al (2010) Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: effects on locomotor activity. Behav Brain Res 211:148–155

    Article  PubMed  CAS  Google Scholar 

  17. Karcz-Kubicha M, Antoniou K, Terasmaa A et al (2003) Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacology 28:1281–1291

    Article  PubMed  CAS  Google Scholar 

  18. Costa MS, Ardais AP, Fioreze GT et al (2012) Treadmill running frequency on anxiety and hippocampal adenosine receptors density in adult and middle-aged rats. Prog Neuropsychopharmacol Biol Psychiatry 36:198–204

    Article  PubMed  CAS  Google Scholar 

  19. Casteels C, Vermaelen P, Nuyts J et al (2006) Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med 47:1858–1866

    PubMed  Google Scholar 

  20. Alexoff DL, Vaska P, Marsteller D et al (2003) Reproducibility of 11C-raclopride binding in the rat brain measured with the microPET R4: effects of scatter correction and tracer specific activity. J Nucl Med 44:815–822

    PubMed  CAS  Google Scholar 

  21. Aznavour N, Benkelfat C, Gravel P et al (2009) MicroPET imaging of 5-HT1A receptors in rat brain: a test–retest [18F]MPPF study. Eur J Nucl Med Mol Imaging 36:53–62

    Article  PubMed  CAS  Google Scholar 

  22. Casteels C, Bormans G, van Laere K (2010) The effect of anaesthesia on [18F]MK-9470 binding to the type 1 cannabinoid receptor in the rat brain. Eur J Nucl Med Mol Imaging 37:1164–1173

    Article  PubMed  CAS  Google Scholar 

  23. Elfving B, Bjornholm B, Knudsen GM (2003) Interference of anaesthetics with radioligand binding in neuroreceptor studies. Eur J Nucl Med Mol Imaging 30:912–915

    Article  PubMed  CAS  Google Scholar 

  24. Kilbourn MR, Ma B, Butch ER, Quesada C, Sherman PS (2007) Anesthesia increases in vivo N-([18F]fluoroethyl)piperidinyl benzilate binding to the muscarinic cholinergic receptor. Nucl Med Biol 34:479–482

    Article  PubMed  CAS  Google Scholar 

  25. Crema LM, Pettenuzzo LF, Schlabitz M et al (2013) The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors. Physiol Behav 109:1–7

    Article  PubMed  CAS  Google Scholar 

  26. Svenningsson P, Fredholm BB (1997) Glucocorticoids regulate the expression of adenosine A1 but not A2A receptors in rat brain. J Pharmacol Exp Ther 280:1094–1101

    PubMed  CAS  Google Scholar 

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Acknowledgments

Magdalene Vögeling, Dina Alghzawi, Tanja Juraschek, Larissa Damm, and Michaela Bohlen are gratefully acknowledged for excellent technical assistance, and Andreas Matusch for proofreading the manuscript. We thank Nikola Kornadt-Beck for the fruitful discussions and valuable support. Johannes Ermert and Heinz H. Coenen are gratefully acknowledged for the supply of the radioligand.

Conflict of Interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich GmbH, 52425, Jülich, Germany

    Tina Kroll, David Elmenhorst, Angela Weisshaupt, Simone Beer & Andreas Bauer

  2. Neurological Department, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Andreas Bauer

Authors
  1. Tina Kroll
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  2. David Elmenhorst
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  3. Angela Weisshaupt
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  4. Simone Beer
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  5. Andreas Bauer
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Correspondence to Tina Kroll.

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Kroll, T., Elmenhorst, D., Weisshaupt, A. et al. Reproducibility of Non-Invasive A1 Adenosine Receptor Quantification in the Rat Brain Using [18F]CPFPX and Positron Emission Tomography. Mol Imaging Biol 16, 699–709 (2014). https://doi.org/10.1007/s11307-014-0729-0

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  • DOI: https://doi.org/10.1007/s11307-014-0729-0

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