title: Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography.
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 = 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.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: J J
authors.initials: JJ
authors.lastname: Frost
authors.forename: K H
authors.initials: KH
authors.lastname: Douglass
authors.forename: H S
authors.initials: HS
authors.lastname: Mayberg
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: J M
authors.initials: JM
authors.lastname: Links
authors.forename: A A
authors.initials: AA
authors.lastname: Wilson
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: W C
authors.initials: WC
authors.lastname: Crozier
authors.forename: H N
authors.initials: HN
authors.lastname: Wagner
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009270:Naloxone; D009778:Occipital Lobe / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D013788:Thalamus / Q000098:blood supply / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D011957:Receptors, Opioid; D009270:Naloxone; C017114:carfentanil; D005283:Fentanyl