Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography

J. J. Frost, K. H. Douglass, H. S. Mayberg, R. F. Dannals, J. M. Links, A. A. Wilson, H. T. Ravert, W. C. Crozier, H. N. Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

[11C]-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of [11C]-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = B(max)/k(D) was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 ± 0.92 to 0.26 ± 0.13 in the thalamus (p<0.01) and from 1.8 ± 0.33 to 0.16 ± 0.065 in the frontal cortex (p<0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: region/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n=20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

Original languageEnglish (US)
Pages (from-to)398-409
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume9
Issue number3
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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