Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on in vivo L-[β-11C]DOPA turnover in the rat striatum with infusion of L-tyrosine

  • H. Tsukada
  • K. -J. Lindner
  • P. Hartvig
  • Y. Tani
  • P. Bjurling
  • T. Kihlberg
  • G. Westerberg
  • Y. Watanabe
  • B. Långström
Full Papers

Summary

L-[11C]DOPA, combined with positron emission tomography (PET), has made possible the assessment of dopamine turnover in vivo. Before the evaluation of PET study with L-[11C]DOPA in the primate, the effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and/or L-tyrosine infusion on L-[11C]DOPA turnover was analyzed in the rat striatal tissue and in the striatal extracellular fluid using microdialysis. L-[11C]DOPA was rapidly taken up into the brain after intravenous injection and converted to [11C]dopamine, [11C]DOPAC and [11C]HVA in the striatal tissue. Small amount of 3-O-methyl-[11C]DOPA, a product of DOPA by 3-O-methylation in peripheral tissues, was also detected in the striatal tissue. The striatum/cerebellum ratio of total radioactivity uptake was linear against time up to 40 min after L-[11C]DOPA injection. The uptake ratio, increased by 6R-BH4 administration, was further increased by L-tyrosine infusion. The in vivo microdialysis technique was further applied to determine L-[11C]DOPA and its metabolites in striatal extracellular fluid (ECF). The peripheral administration of 6R-BH4 (50mg/kg) induced elevation of [11C]DOPA concentration in ECF in the early phase after injection, following higher radioactivity in [11C]dopamine and [11C]HVA fractions than those in control animals at late phase. The 6R-BH4-induced elevation of [11C]DOPA uptake and the radioactivity of its metabolites was further enhanced by the continuous infusion of L-tyrosine at a dose of 1.0 μmol/min/kg. L-Tyrosine infusion alone did not induce the elevation of radioactivity. The results suggest that [11C]DOPA might be a useful probe to evaluate the effect of 6R-BH4 and/or L-tyrosine loading in the primate.

Keywords

Tetrahydrobiopterin L-[β-11C]DOPA dopamine L-tyrosine microdialysis 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • H. Tsukada
    • 1
  • K. -J. Lindner
    • 2
  • P. Hartvig
    • 2
  • Y. Tani
    • 3
  • P. Bjurling
    • 4
  • T. Kihlberg
    • 4
  • G. Westerberg
    • 4
  • Y. Watanabe
    • 5
  • B. Långström
    • 4
  1. 1.Hamamatsu Photonics K. K.Central Research Laboratory PET CenterShizuokaJapan
  2. 2.Hospital Pharmacy, University HospitalUppsala UniversityUppsalaSweden
  3. 3.Suntory Institute for Biomedical ResearchOsakaJapan
  4. 4.Uppsala University PET CenterUppsala UniversityUppsalaSweden
  5. 5.Department of NeuroscienceOsaka Bioscience InstituteOsakaJapan

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