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; p. 398
• Main Authors: Frost, J J, Douglass, K H, Mayberg, H S, Dannals, R F, Links, J M, Wilson, A A, Ravert, H T, Crozier, W C, Wagner, Jr, H N
• Format: Journal Article
• Language: English
• Published: United States 01-06-1989
• Subjects: Adult; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Fentanyl - analogs & derivatives; Fentanyl - metabolism; Frontal Lobe - metabolism; Humans; Kinetics; Male; Naloxone; Occipital Lobe - metabolism; Receptors, Opioid - metabolism; Thalamus - blood supply; Thalamus - metabolism; Tomography, Emission-Computed
• ISSN: 0271-678X
• 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 less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 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.