Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers

  • Valerie Treyer
  • Johannes Streffer
  • Simon M. Ametamey
  • Andrea Bettio
  • Peter Bläuenstein
  • Mark Schmidt
  • Fabrizio Gasparini
  • Uta Fischer
  • Christoph Hock
  • Alfred Buck
Original article

Abstract

Introduction

In this study, we assessed the whole-body biodistribution and radiation dosimetry of the new glutamatergic ligand 11C-ABP688. This ligand binds specifically to the metabotropic glutamatergic receptor of subtype 5 (mGluR5).

Materials and methods

The study included five healthy male volunteers aged 20-29 years. After intravenous injection of 240-260 MBq, a series of four to ten whole-body positron emission tomography/computed tomography scans were initiated, yielding 60-80 min of data. Residence times were then calculated in the relevant organs, and the software packages Mirdose and Olinda were used to calculate the absorbed radiation dose and the effective dose equivalent.

Results

Of the excreted 11C activity at 1 hour, approximately 80% were eliminated via the hepato-biliary pathway and 20% through the urinary tract. The absorbed dose (mGy/MBq) was highest in the liver (1.64 E -2 ± 5.08 E -3), gallbladder (8.13 E -3 ± 5.6 E -3), and kidneys (7.27 E -3 ± 2.79 E -3). The effective dose equivalent was 3.68 ± 0.84 microSv/MBq. Brain uptake in the areas with high mGluR5 density was 2-3 (SUV). The agreement between the values obtained from Mirdose and the Olinda was excellent.

Conclusion

11C-ABP688 is a very promising ligand for the investigation of mGluR5 receptors in humans. Brain uptake is high and the effective dose equivalent so low that serial examinations in the same subject seem feasible.

Keywords

11C-ABP688 Metabotropic glutamate receptor subtype 5 Whole-body PET/CT Dosimetry 

References

  1. 1.
    Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S. Sequence and expression of a metabotropic glutamate receptor. Nature 1991;349(6312):760-5.CrossRefPubMedGoogle Scholar
  2. 2.
    Gasparini F, Lingenhohl K, Stoehr N, Flor PJ, Heinrich M, Vranesic I, et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999;38(10):1493-503.CrossRefPubMedGoogle Scholar
  3. 3.
    Kuhn R, Pagano A, Stoehr N, Vranesic I, Flor PJ, Lingenhohl K, et al. In vitro and in vivo characterization of MPEP, an allosteric modulator of the metabotropic glutamate receptor subtype 5: review article. Amino Acids 2002;23(1-3):207-11.CrossRefPubMedGoogle Scholar
  4. 4.
    Spooren W, Gasparini F. mGlu5 receptor antagonists: a novel class of anxiolytics? Drug News Perspect 2004;17:251-7.CrossRefPubMedGoogle Scholar
  5. 5.
    Spooren WP, Vassout A, Neijt HC, Kuhn R, Gasparini F, Roux S, et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 2000;295(3):1267-75.PubMedGoogle Scholar
  6. 6.
    Tatarczynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Gasparini F, Kuhn R, et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 2001;132(7):1423-30.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hamill TG, Krause S, Ryan C, Bonnefous C, Govek S, Seiders TJ, et al. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers. Synapse 2005;56(4):205-16.CrossRefPubMedGoogle Scholar
  8. 8.
    Ametamey SM, Kessler LJ, Honer M, Wyss MT, Hintermann S, Auberson YP, et al. Radiosynthesis and preclinical evaluation of [11C]-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5 (mGluR5). J Nucl Med 2005;47:698-705.Google Scholar
  9. 9.
    Stabin MG. Mirdose: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996;37(3):538-46.PubMedGoogle Scholar
  10. 10.
    Stabin MG, Sparks RB, Crowe E. Olinda/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46(6):1023-7.PubMedGoogle Scholar
  11. 11.
    Ametamey SM, Treyer V, Streffer J, Wyss MT, Schmidt M, Blagoev M, et al. Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688. J Nucl Med 2007;48(2):247-52.PubMedGoogle Scholar
  12. 12.
    Ribeiro MJ, Ricard M, Bourgeois S, Lievre MA, Bottlaender M, Gervais P, et al. Biodistribution and radiation dosimetry of [11C]raclopride in healthy volunteers. Eur J Nucl Med Mol Imaging 2005;32(8):952-8.CrossRefPubMedGoogle Scholar
  13. 13.
    Bottlaender M, Valette H, Roumenov D, Dolle F, Coulon C, Ottaviani M, et al. Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers. J Nucl Med 2003;44(4):596-601.PubMedGoogle Scholar
  14. 14.
    Obrzut SL, Koren AO, Mandelkern MA, Brody AL, Hoh CK, London ED. Whole-body radiation dosimetry of 2-[18F]Fluoro-A-85380 in human PET imaging studies. Nucl Med Biol 2005;32(8):869-74.CrossRefPubMedGoogle Scholar
  15. 15.
    Seneca N, Andree B, Sjoholm N, Schou M, Pauli S, Mozley PD, et al. Whole-body biodistribution, radiation dosimetry estimates for the PET norepinephrine transporter probe (S,S)-[18F]FMeNER-D2 in non-human primates. Nucl Med Commun 2005;26(8):695-700.CrossRefPubMedGoogle Scholar
  16. 16.
    Slifstein M, Hwang DR, Martinez D, Ekelund J, Huang Y, Hackett E, et al. Biodistribution and Radiation dosimetry of the dopamine D2 Ligand 11C-raclopride determined from human whole-body PET. J Nucl Med 2006;47(2):313-9.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Valerie Treyer
    • 1
  • Johannes Streffer
    • 2
  • Simon M. Ametamey
    • 3
  • Andrea Bettio
    • 3
  • Peter Bläuenstein
    • 3
  • Mark Schmidt
    • 4
  • Fabrizio Gasparini
    • 5
  • Uta Fischer
    • 2
  • Christoph Hock
    • 2
  • Alfred Buck
    • 1
  1. 1.PET Center, Division of Nuclear MedicineUniversity Hospital ZurichZurichSwitzerland
  2. 2.Division of Psychiatry ResearchUniversity of ZurichZurichSwitzerland
  3. 3.Department of Chemistry and Applied Biosciences of ETHCenter for Radiopharmaceutical Science of ETH, PSI and USZZurichSwitzerland
  4. 4.Novartis Pharma AGBaselSwitzerland
  5. 5.Novartis Institutes for Biomedical ResearchBaselSwitzerland

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