Advertisement

Stability of α-[11C]methyl-l-tryptophan brain trapping in healthy male volunteers

  • Pedro Rosa-Neto
  • Mirko Diksic
  • Marco Leyton
  • Shadreck Mzengeza
  • Chawki Benkelfat
Original Article

Abstract

Purpose

The purpose of this study was to assess the reproducibility in healthy volunteers of α-[11C]methyl-l-tryptophan (α[11C]MT) brain trapping imaging with positron emission tomography (PET), using volumes of interest (VOIs) and voxel-based image analysis.

Methods

Six right-handed healthy male volunteers (34.3±10.9 years) with a negative family history for psychiatric disorders were scanned twice in the resting condition, 22±17 days apart. An unbiased semiautomatic segmentation of the brain was used to define VOIs. The trapping constant K* (ml g−1 min−1) for α[11C]MT was calculated for the whole brain and seven brain regions using the graphical method for irreversible tracers. In addition, parametric maps of K* were obtained from dynamic scans using the same method. Comparison of test and retest K* functional images was performed using SPM99. Student’s paired t statistic was applied for comparisons of α[11C]MT brain trapping in a priori selected VOIs.

Results

α[11C]MT brain trapping in VOIs showed a mean variability 2.6±1.8% (0.3–5%) for absolute and 1.5±2.1% (1.4–4.1%) for normalized K*. Intraclass correlations between test and retest conditions were 0.61±0.34 for absolute K* values and 0.73±0.20 for K* values normalized by global mean. SPM99 analysis using a height threshold of p=0.05 (two tailed) and an extent threshold of 100 voxels showed no significant differences between scans.

Conclusion

Rest measurements in healthy male volunteers of the trapping constant for α[11C]MT, using PET, appeared to be stable during an average interval of 3 weeks.

Keywords

PET α[11C]MT  Brain trapping Serotonin synthesis Test–retest 

Notes

Acknowledgements

This research was supported in part by grants from the NIH, CIHR, and FRSQ.

References

  1. 1.
    Hagberg GE, Torstenson R, Marteinsdottir I, Fredrikson M, Langstrom B, Blomqvist G. Kinetic compartment modeling of [11C]-5-hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab 2002;22:1352–66CrossRefPubMedGoogle Scholar
  2. 2.
    Frazer A, Hensler J. Serotonin. In: Siegel GJ, Agranoff BW, Albers RW, et al., eds. Basic neurochemistry, 5th edn. Vol. 3. New York: Raven Press; 1995Google Scholar
  3. 3.
    Diksic M, Nagahiro S, Sourkes TL, Yamamoto YL. A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model. J Cereb Blood Flow Metab 1990;10:1–12PubMedGoogle Scholar
  4. 4.
    Muzik O, Chugani DC, Chakraborty P, Mangner T, Chugani HT. Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo. J Cereb Blood Flow Metab 1997;17:659–69CrossRefPubMedGoogle Scholar
  5. 5.
    Diksic M, Young SN. Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem 2001;78:1185–200CrossRefPubMedGoogle Scholar
  6. 6.
    Cohen Z, Tsuiki K, Takada A, Beaudet A, Diksic M, Hamel E. In vivo-synthesized radioactively labelled alpha-methyl serotonin as a selective tracer for visualization of brain serotonin neurons. Synapse 1995;21:21–8CrossRefPubMedGoogle Scholar
  7. 7.
    Missala K, Sourkes TL. Functional cerebral activity of an analogue of serotonin formed in situ. Neurochem Int 1988;12:209–14CrossRefGoogle Scholar
  8. 8.
    WHO. Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. In: 18th World Medical Assembly. Helsinki: World Medical Association; 1964Google Scholar
  9. 9.
    Nishizawa S, Leyton M, Okazawa H, Benkelfat C, Mzengeza S, Diksic M. Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan. J Cereb Blood Flow Metab 1998;18:1121–9CrossRefPubMedGoogle Scholar
  10. 10.
    First MB, Spitzer RL, Gibbon M, William JBW. Structured clinical interview for the DSM-IV-TR axis I disorders—patient edition (SCID-I/P, version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute; 1998Google Scholar
  11. 11.
    Nurnberger JI Jr, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG, Harkavy-Friedman J, et al. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 1994;51:849–59; discussion 863–864PubMedGoogle Scholar
  12. 12.
    Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3:1–7PubMedGoogle Scholar
  13. 13.
    Diksic M, Tohyama Y, Takada A. Brain net unidirectional uptake of alpha-[14C]methyl-L-tryptophan (alpha-MTrp) and its correlation with regional serotonin synthesis, tryptophan incorporation into proteins, and permeability surface area products of tryptophan and alpha-MTrp. Neurochem Res 2000;25:1537–46CrossRefPubMedGoogle Scholar
  14. 14.
    Chugani DC, Chugani HT. PET: mapping of serotonin synthesis. Adv Neurol 2000;83:165–71PubMedGoogle Scholar
  15. 15.
    Shoaf SE, Carson RE, Hommer D, Williams WA, Higley JD, Schmall B, et al. The suitability of [11C]-alpha-methyl-L-tryptophan as a tracer for serotonin synthesis: studies with dual administration of [11C] and [14C] labeled tracer. J Cereb Blood Flow Metab 2000;20:244–52CrossRefPubMedGoogle Scholar
  16. 16.
    Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackoviak RS. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 1995;2:189–210CrossRefGoogle Scholar
  17. 17.
    Seibyl JP, Laruelle M, van Dyck CH, Wallace E, Baldwin RM, Zoghbi S, et al. Reproducibility of iodine-123-beta-CIT SPECT brain measurement of dopamine transporters. J Nucl Med 1996;37:222–8PubMedGoogle Scholar
  18. 18.
    Okazawa H, Diksic M. Image generation of serotonin synthesis rates using alpha-methyltryptophan and PET. J Comput Assist Tomogr 1998;22:777–85CrossRefPubMedGoogle Scholar
  19. 19.
    Okazawa H, Leyton M, Benkelfat C, Mzengeza S, Diksic M. Statistical mapping analysis of serotonin synthesis images generated in healthy volunteers using positron-emission tomography and alpha-[11C]methyl-L-tryptophan. J Psychiatry Neurosci 2000;25:359–70PubMedGoogle Scholar
  20. 20.
    Collins DL, Neelin P, Peters TM, Evans AC. Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 1994;18:192–205PubMedGoogle Scholar
  21. 21.
    Okazawa H, Diksic M. Image generation of serotonin synthesis rates using alpha-methyltryptophan and PET. J Comput Assist Tomogr 1998;22 5:777–85CrossRefPubMedGoogle Scholar
  22. 22.
    Leyton M, Okazawa H, Diksic M, Paris J, Rosa P, Mzengeza S, et al. Brain regional [11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder. Am J Psychiatry 2001;158:775–82CrossRefPubMedGoogle Scholar
  23. 23.
    Collins LG, Evans AC. Animal: validation and applications of non-linear registration-based segmentation. Int J Pattern Recogn Art Intell 1997;11:1271–94CrossRefGoogle Scholar
  24. 24.
    Collins DL, Zijdenbos AP, Barré WFC, Evans AC. ANIMAL+INSECT: inproved cortical structure segmentation. In: Kuba A, Samal M, Todd-Pokropek A, eds. Proc. of the annual symposium on information processing in medical imaging. Vol. 1613. Springer, 1999;210–23Google Scholar
  25. 25.
    Sled JG, Zijdenbos AP, Evans AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imag 1998;17:87–97CrossRefGoogle Scholar
  26. 26.
    Zijdenbos A, Forghani R, Evans A. Automatic quantification of MS lesions in 3D MRI brain data sets: validation of INSECT. In: Proceedings of International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). Berlin Heidelberg New York: Springer; 1998Google Scholar
  27. 27.
    Maquet P, Dive D, Salmon E, von Frenckel R, Franck G. Reproducibility of cerebral glucose utilization measured by PET and the [18F]-2-fluoro-2-deoxy-d-glucose method in resting, healthy human subjects. Eur J Nucl Med 1990;16:267–73CrossRefPubMedGoogle Scholar
  28. 28.
    Melega WP, Raleigh MJ, Stout DB, DeSalles AA, Cherry SR, Blurton-Jones M, et al. Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys. Exp Neurol 1996;141:318–29CrossRefPubMedGoogle Scholar
  29. 29.
    Koeppe RA, Mangner T, Betz AL, Shulkin BL, Allen R, Kollros P, et al. Use of [11C]aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain. J Cereb Blood Flow Metab 1990;10:727–39PubMedGoogle Scholar
  30. 30.
    Shoaf SE, Carson R, Hommer D, Williams W, Higley JD, Schmall B, et al. Brain serotonin synthesis rates in rhesus monkeys determined by [11C]alpha-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations. Neuropsychopharmacology 1998;19:345–53Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Pedro Rosa-Neto
    • 1
    • 2
  • Mirko Diksic
    • 1
  • Marco Leyton
    • 1
    • 2
  • Shadreck Mzengeza
    • 1
  • Chawki Benkelfat
    • 1
    • 2
  1. 1.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Department of PsychiatryMcGill UniversityMontrealCanada

Personalised recommendations