Multicompartmental Analysis of [11C]-Carfentanil Binding to Opiate Receptors in Humans Measured by Positron Emission Tomography

• Published in: Journal of cerebral blood flow and metabolism Vol. 9; no. 3; pp. 398 - 409
• Main Authors: Frost, J. J., Douglass, K. H., Mayberg, H. S., Dannals, R. F., Links, J. M., Wilson, A. A., Ravert, H. T., Crozier, William C., Wagner, H. N.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.1989; Lippincott Williams & Wilkins
• Subjects: Adult; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Fentanyl - analogs & derivatives; Fentanyl - metabolism; Frontal Lobe - metabolism; Humans; Kinetics; Male; Medical sciences; Naloxone; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Occipital Lobe - metabolism; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Opioid - metabolism; Thalamus - blood supply; Thalamus - metabolism; Tomography, Emission-Computed; Thalamus; Frontal cortex; Mu opiate receptors; Positron emission tomography; Occipital cortex; [11C]-Carfentanil; Human; Brain; Agonist; Biological fixation; Intravenous administration; Compartment model; Opiates; Normal; Opiate receptor μ
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.1989.59

[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 = Bmax/kd 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: regions/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.