Kinetic modeling of [11C]raclopride: Combined PET-microdialysis studies

Christopher J. Endres, Bhaskar S. Kolachana, Richard C. Saunders, Tom Su, Daniel Weinberger, Alan Breier, William C. Eckelman, Richard E. Carson

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

The in vivo binding of D2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [11C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.

Original languageEnglish (US)
Pages (from-to)932-942
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number9
DOIs
StatePublished - Sep 1997
Externally publishedYes

Keywords

  • Compartmental models
  • D receptors
  • Microdialysis
  • Positron emission tomography
  • Raclopride

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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    Endres, C. J., Kolachana, B. S., Saunders, R. C., Su, T., Weinberger, D., Breier, A., Eckelman, W. C., & Carson, R. E. (1997). Kinetic modeling of [11C]raclopride: Combined PET-microdialysis studies. Journal of Cerebral Blood Flow and Metabolism, 17(9), 932-942. https://doi.org/10.1097/00004647-199709000-00002